Vitamin D Analogs Versus Native Vitamin D in Preventing Bone Loss and Osteoporosis-Related Fractures: A Comparative Meta-analysis

It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to preserve their bone mineral density (BMD) and to avoid fragility fractures. We designed the present study to compare the effects of native vitamin D to its hydroxylated analogs alfacalcidol 1-(OH)D and calcitriol 1,25(OH)₂D. All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, and a hand search of abstracts and references lists. The study period January 1985 to January 2003. Data were abstracted by two investigators, and methodological quality was assessed in a similar manner. Heterogeneity was extensively investigated. Results were expressed as effect-size (ES) for bone loss and as rate difference (RD) for fracture while allocated to active treatment or control. Publication bias was investigated. Fourteen studies of native vitamin D, nine of alfacalcidol, and ten of calcitriol fit the inclusion criteria. The two vitamin D analogs appeared to exert a higher preventive effect on bone loss and fracture rates in patients not exposed to glucocorticoids. With respect to BMD, vitamin D analogs versus placebo studies had an ES of 0.36 (P < 0.0001), whereas native vitamin D versus placebo had an ES of 0.17 (P = 0.0005), the interclass difference being highly significant (ANOVA-1, P < 0.05). When restricted to the lumbar spine, this intertreatment difference remained significant: ES = 0.43 (P = 0.0002) for vitamin D analogs and ES = 0.21 (P = 0.001) for native vitamin D (analysis of variance [ANOVA-1], P = 0.047). There were no significant differences regarding their efficacies on other measurement sites (ANOVA-1, P = 0.36). When comparing the adjusted global relative risks for fracture when allocated to vitamin D analogs or native vitamin D, alfacalcidol and calcitriol provided a more marked preventive efficacy against fractures: RD = 10% (95% Confidence interval [CI-2] to 17) compared to RD = 2% (95% CI, 1 to 2), respectively. The analysis of the spinal and nonspinal showed that fracture rates differed between the two classes, thereby confirming the benefits of vitamin D analogs, with significant 13.4% (95% CI 7.7 to 19.8) and. 6% (95% CI 1 to 12) lower fracture rates for vitamin D analogs, respectively. In patients receiving corticosteroid therapy, both treatments provided similar global ESs for BMD: ES = 0.38 for vitamin D analogs and ES = 0.41 for native vitamin D (ANOVA-1, P = 0.88). When restriced to spinal BMD, D analogs provided significant effects, whereas native vitamin D did not: ES = 0.43 (P < 0.0001) and ES = 0.33 (P = 0.21), respectively. The intertreatment difference was nonsignificant (ANOVA-1, P = 0.52). Neither D analogs for native vitamin D significantly prevented fractures in this subcategory of patients: RD = 2.6 (95%CI, –9.5 to 4.3) and RD = 6.4 (95%CI, –2.3 to 10), respectively. In head-to-head studies comparing D analogs and native vitamin D in patients receiving corticosteroids, significant effects favoring D analogs were found for femoral neck BMD: ES = 0.31 at P = 0.02 and spinal fractures: RD = 15% (95%CI, 6.5 to 25). Publication bias was not significant. Our analysis demonstrates a superiority of the D analogs atfacalcidol and calcitriol in preventing bone loss and spinal fractures in primary osteoporosis, including postmenopausal women. In corticosteroid-induced osteoporosis, the efficacy of D analogs differed depending on the comparative approach: indirect comparisons led to nonsignificant differences, whereas direct comparison did provide significant differences. In this setting, D analogs seem to prevent spinal fractures to a greater extent than do native vitamin D, but this assumption should be confirmed on a comprehensive basis in multiarm studies including an inactive comparator.     

Vitamin D Therapy of Osteoporosis: Plain Vitamin D Therapy Versus Active Vitamin D Analog (D-Hormone) Therapy

Normal intestinal calcium (Ca) absorption is an essential feature of bone homeostasis. As with many other organ systems, intestinal Ca absorption declines with aging, and this is one pathological factor that has been identified as a cause of senile osteoporosis in the elderly. This abnormality leads to secondary hyperparathyroidism, which is characterized by high serum parathyroid hormone (PTH) and an increase in bone resorption. Secondary hyperparathyroidism due to poor intestinal Ca absorption has been implicated not only in senile osteoporosis but also in age-related bone loss. Accordingly, in population-based studies, there is a gradual increase in serum PTH from about 20 years of age onward, which constitutes a maximum increase at 80 years of age of 50% of the basal value seen at 30 years of age. The cause of the increase in PTH is thought to be partly due to impaired intestinal Ca absorption that is associated with aging, a cause that is not entirely clear but at least in some instances is related to some form of vitamin D deficiency. There are three types of vitamin D deficiency: (1) primary vitamin D deficiency, which is due to a deficiency of vitamin D, the parent compound; (2) a deficiency of 1,25(OH)₂D₃ resulting from decreased renal production of 1,25(OH)₂D₃; and (3) resistance to 1,25(OH)₂D₃ action owing to decreased responsiveness to 1,25(OH)₂D₃ of target tissues. The cause for the resistance to 1,25(OH)₂D₃ could be related to the finding that the vitamin D receptor level in the intestine tends to decrease with age. All three types of deficiencies can occur with aging, and each has been implicated as a potential cause of intestinal Ca malabsorption, secondary hyperparathyroidism, and senile osteoporosis. There are two forms of vitamin D replacement therapies: plain vitamin D therapy and active vitamin D analog (or D-hormone) therapy. Primary vitamin D deficiency can be corrected by vitamin supplements of 1000 U a day of plain vitamin D whereas 1,25(OH)₂D₃ deficiency/resistance requires active vitamin D analog therapy [1,25(OH)₂D₃ or 1α(OH)D₃] to correct the high serum PTH and the Ca malabsorption. In addition, in the elderly, there are patients with decreased intestinal Ca absorption but with apparently normal vitamin D metabolism. Although the cause of poor intestinal Ca absorption in these patients is unclear, these patients, as well as all other patients with secondary hyperparathyroidism (not due to decreased renal function), show a decrease in serum PTH and an increase in Ca absorption in response to therapy with 1,25(OH)₂D₃ or 1α(OH)D₃. In short, it is clear that some form of vitamin D therapy, either plain vitamin D or 1,25(OH)₂D₃ or 1α(OH)D₃, can be used to correct all types of age-dependent impairments in intestinal Ca absorption and secondary hyperparathyroidism during aging. However, from a clinical standpoint, it is important to recognize the type of vitamin D deficiency in patients with senile osteoporosis so that primary vitamin D deficiency can be appropriately treated with plain vitamin D therapy, whereas 1,25(OH)₂D₃ deficiency/resistance will be properly treated with 1,25(OH)₂D₃ or 1α(OH)D₃ therapy. With respect to postmenopausal osteoporosis, there is strong evidence that active vitamin D analogs (but not plain vitamin D) may have bone-sparing actions. However, these effects appear to be results of their pharmacologic actions on bone formation and resorption rather than through replenishing a deficiency.     

健脾方对去势大鼠维生素D代谢的影响

目的采用放射免疫方法与分子生物学方法从VitD代谢的角度探讨健脾方防治原发性骨质疏松症的机制。方法建立卵巢切除致骨质疏松大鼠模型,运用骨组织病理学、血液生物化学等方法综合观察健脾方对模型大鼠骨密度、尿吡啶酚（PYD）和血清骨钙素（BGP）的影响;同时应用放射免疫方法与逆转录聚合酶链式反应观察健脾方对模型大鼠血清1,25（OH）2D3和小肠、肾脏组织维生素D受体基因（VDR mRNA）表达的影响。结果健脾方能升高模型大鼠的骨密度,降低模型大鼠血清1,25（OH）2D3的含量（P〈0.05）,同时能上调模型大鼠小肠、肾脏VDR mRNA的表达。结论健脾方能增强机体对血清1,25（OH）2D3反应敏感性,上调小肠与肾脏VDR mRNA的表达,调节VitD代谢。     

Decrease in bone levels of 1,25-dihydroxyvitamin D in women with subcapital fracture of the femur

Summary In a previous study we were able to show that in women over the age of 45 the level of 1,25-dihydroxyvitamin D (1,25(OH)₂D) in bone, but not in serum, is significantly reduced when compared with younger women. In the present study we measured the concentration of 1,25(OH)₂D in sera and bones of 19 female patients with subcapital fractures of the femur, mean age 78±2 years. We were able to show that serum levels of 1,25(OH)₂D were within the normal range, while bone levels were markedly reduced compared to levels in femoral bone obtained from young female cadavers or to the previously reported levels in non-osteoporotic elderly women. Thus, reduced levels of 1,25(OH)₂D in bones of elderly women may lead, together with other factors, to subcapital fractures.Holder of Prof. T. Reichstein Professorial Chair     

广州地区骨质疏松症患者冬季维生素D水平现状分析

目的调查广州地区冬季骨质疏松症患者体内维生素D(Vit D)水平的状况。方法随机选取2014年12月至2015年2月我院299例年龄≥50岁骨质疏松症患者,采集其清晨空腹静脉血,所有研究对象均采用Cobase 6000型电化学发光仪(瑞士,罗氏诊断)检测血清25-羟维生素D(25(OH)D)和甲状旁腺激素(PTH)水平,日立7180型自动生化分析仪测定钙(Ca)、磷(P)及碱性磷酸酶(ALP)水平。双能X线吸收仪检测腰椎和股骨近端骨密度(BMD),SPSS 16.0软件进行数据分析。结果299例骨质疏松症患者,其中男性患者63例,25(OH)D平均水平为(52.75±17.30)nmol/L,女性患者236例,25(OH)D平均水平(53.97±16.11)nmol/L。其中Vit D正常者仅占3.3%,缺乏者占47.6%,不足者占44.8%,严重不足者占4.3%。这些患者普遍存在着25(OH)D水平不足现象,其中Vit D缺乏和不足所占比例较大,且男女两组的25(OH)D水平无统计学差异。结论本研究显示广州地区冬季骨质疏松症患者25(OH)D不足和缺乏现象较普遍,且无性别差异,补充足量Vit D,需要重视及积极治疗,定期监测25(OH)D水平,为临床骨质疏松症的防治提供一定的数据参考。     

The Advantage of Alfacalcidol Over Vitamin D in the Treatment of Osteoporosis

Although alfacalcidol is widely used in the treatment of osteoporosis, its mechanism of action in bone is not fully understood. Alfacalcidol stimulates intestinal calcium (Ca) absorption, increases urinary Ca excretion and serum Ca levels, and suppresses parathyroid hormone (PTH) secretion. It remains to be clarified, especially under vitamin D-replete conditions, whether alfacalcidol exerts skeletal effects solely via these Ca-related effects, whether the resultant suppression of PTH is a prerequisite for the skeletal actions of alfacalcidol, and, by inference, whether alfacalcidol has an advantage over vitamin D in the treatment of osteoporosis. To address these issues, we (1) compared the effects of alfacalcidol p.o. (0.025–0.1 μg/kg BW) vis-à-vis vitamin D₃ (50–400 μg/kg BW) on bone loss in 8-month-old, ovariectomized (OVX) rats as a function of their Ca-related effects, and (2) examined whether the skeletal effects of alfacalcidol occur independently of suppression of PTH, using parathyroidectomized (PTX) rats continuously infused with hPTH(1–34). The results indicate that (1) in OVX rats, alfacalcidol increases BMD and bone strength more effectively than vitamin D₃ at given urinary and serum Ca levels: larger doses of vitamin D₃ are required to produce a similar BMD-increasing effect, in the face of hypercalcemia and compromised bone quality; (2) at doses that maintain serum Ca below 10 mg/dl, alfacalcidol suppresses urinary deoxypyridinoline excretion more effectively than vitamin D₃; and (3) alfacalcidol is capable of increasing bone mass in PTX rats with continuous infusion of PTH, and therefore acts independently of PTH levels. It is suggested that alfacalcidol exerts bone-protective effects independently of its Ca-related effects, and is in this respect superior to vitamin D₃, and that the skeletal actions of alfacalcidol take place, at least in part, independently of suppression of PTH. Together, these results provide a rationale for the clinical utility of alfacalcidol and its advantage over vitamin D₃ in the treatment of osteoporosis.     

维生素K2联合维生素D3治疗青壮年早期膝骨关节炎的研究

目的探讨维生素K2联合维生素D3治疗青壮年早期膝骨关节炎的作用。 方法2016年1月至2017年6月广州医科大学附属第二医院骨外科门诊因膝关节疼痛的患者共387例。符合早期膝骨关节炎(KOA)的青壮年患者132例,均给予相同剂量的维生素K2和维生素D3(VD)口服,随访6个月,通过观察服药前后血清25-OH-VD、血清总Ⅰ型胶原氨基端延长肽(P1NP)检测、视觉模拟评分(VAS)及股四头肌肌力的比较,维生素K2和维生素D3治疗前后各指标采用配对t检验评价治疗效果。 结果随访6个月后,血清25-OH-VD(t ＝ 2.664)、血清P1NP(t＝3.265 )的水平及股四头肌肌力(最大肌力t ＝3.005;平均肌力t ＝2.564)均较用药前增加(均为P<0.05),总体VAS评分较用药前下降( t＝3.762,P<0.05)。同时治疗前发现其中33例患者膝关节MRI检查中提示胫骨平台或股骨内侧髁存在不同程度的软骨丢失和骨髓水肿。 结论维生素K2和维生素D3联合应用能改善青壮年膝骨关节炎患者的骨营养代谢,并促进成骨作用从而改善膝关节疼痛症状和活动能力。因此对于青壮年KOA,应该早期干预治疗,从而起到抑制作用。     

Vitamin D Receptor Alleles and Bone's Response to Physical Activity

The objective of this prospective controlled study was to determine whether the osteogenic response of bone to mechanical loading is dependent on the vitamin D receptor (VDR) polymorphism. Thirty-five healthy premenopausal women took part in a progressive, high-impact exercise three times a week for a period of 18 months and 45 women served as nonexercising controls. The trainees were divided into three groups: bb (n = 12, 34%); Bb (n = 16, 46%); BB (n = 7, 20%) according to polymorphism at the gene encoding the VDR (BB representing subjects without the restriction enzyme BsmI sites on the two VDR gene alleles). Bone mineral content (BMC) and areal bone mineral density (BMD) were measured at the lumber spine, proximal femur, knee, calcaneus, and dominant distal radius before the beginning of the exercise regimen and at 12 and 18 months of training using dual-energy x-ray absorptiometry (DXA). As an indicator of the total osteogenic effect of the training, ΣBMC was derived by summing up the BMC values of the loaded sites (i.e., the lower limb sites and the lumbar spine). The mean ΣBMC increased 2.0% in the bb group, 3.0% in the Bb group, and 2.8% in the BB group (P= 0.184 for the intergroup difference), but only 0.8% in the controls (exercisers versus controls, P < 0.001). Individuals with the BB genotype of the VDR gene, subjects with whom the BMC can be lower than normal and whose bones can be less responsive to pharmacological therapies than bones of the other individuals, seem to have as good osteogenic response to mechanical loading as subjects with other VDR genotypes. Thus, irrespective of the VDR genotype, physical activity seems to be beneficial for bones of premenopausal women. Received: 14 May 1997 / Accepted: 14 November 1997     

Vitamin D3 and avian bonein vitro: Stimulation of calcium movement into Japanese quail calvaria

Summary Addition of 1,25 dihydroxyvitamin D₃ (1,25(OH)₂D₃) to cultured neonatal mouse calvaria has consistently led to bone resorption as determined by an increase in medium calcium. No such effect on avian bone has been widely reported. We have tested thein vitro effects of 1,25(OH)₂D₃ on 48-and 96-hour cultures of calvaria removed from both sexes of Japanese quail at various ages. No effect of 1,25(OH)₂D₃ on net calcium movement was seen in cultures of calvaria removed from neonatal (5-day), 1-week, and 2-week-old quail. In cultures of calvaria from 6-week-old female quail, addition of 1,25(OH)₂D₃ resulted in afall in medium total and ionic calcium concentrations after 48 and 96 hours of incubation, indicating an uptake of calcium by the bones. A maximal effect was seen at 1 ×10⁻⁷M 1,25(OH)₂D₃. Bones removed from male and female quail showed no difference in response between the sexes. Bones removed from 5-,4-, and 3-week-old male and female quail exhibited a progressively decreasing response with decreasing age. After 6 weeks of age female birds begin to exhibit hypercalcemia associated with reproductive activity. Bones removed from 7-and 8-week-old female quail responded to 1,25(OH)₂D₃ in a similar fashion whether they were hypercalcemic (7 weeks, 20.3 mg/dl; 8 weeks, 31.7 mg/dl), or normocalcemic (10.1 mg/dl). This stimulatory effect of 1,25(OH)₂D₃ on calcium uptake by avian bone is in sharp contrast to the hormone's effect in cultures of perinatal mammalian bones, which consistently respond to 1,25(OH)₂D₃ by releasing calcium into the medium. To our knowledge, these results demonstrate for the first time a directin vitro effect of 1,25(OH)₂D₃ on calcium movement into bone.     

Vitamin D insufficiency does not affect response of bone mineral density to alendronate

Summary  We investigated whether osteoporosis therapy with alendronate in postmenopausal patients is equally effective in patients who are vitamin D insufficient as in those who are vitamin D sufficient. We found that vitamin D insufficiency is common among patients with low bone density but that vitamin D insufficiency did not impair response to alendronate. Introduction  Treatment of vitamin D deficiency leads to significant improvements in bone mineral density (BMD); however, whether insufficiency affects BMD’s response to bisphosphonate therapy is unknown. Methods  To determine whether vitamin D insufficiency at initiation of alendronate therapy for low BMD affects treatment efficacy, we used data from 1,000 postmenopausal women randomly selected from the vertebral fracture arm (n = 2,027) of the placebo-controlled Fracture Intervention Trial of alendronate. Participants were randomly assigned to placebo (50%) or alendronate therapy and most (83%) to calcium (500 mg/day) and cholecalciferol (250 IU/day). We measured serum 25-hydroxy vitamin D (25OHD) at enrollment, then categorized baseline vitamin D status according to 25OHD concentration ( ≤ 10 ng/ml = deficient; >10 but ≤ 30 ng/ml = insufficient; >30 ng/ml = sufficient) and used linear regression to compare the effects of alendronate treatment among these categories. Results and conclusion  At baseline, participants were vitamin D sufficient (14%), insufficient (83%), and deficient (2%). We found that BMD response to therapy at total hip or spine did not vary by vitamin D status at baseline (p for heterogeneity = 0.6). We determined that vitamin D insufficiency is common among participants with low BMD. However, vitamin D status at initiation of therapy does not affect BMD’s response to alendronate, when it is coadministered with cholecalciferol and calcium. Scholar’s Grant from the National Osteoporosis Foundation (to D.M.A) and National Institutes of Health grant K23 RR020343 (to D.M.A).     

Vitamin D and bone mineral density

Bone mineral density (BMD) at the lumbar spine and the neck of femur and serum concentrations of 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (PTH), alkaline phosphatase, calcium, albumin, creatinine and phosphate were measured in a group of 166 postmenopausal women (30–79 years) attending a bone clinic for bone density measurements. Four subjects with suspected primary hyperparathyroidism were excluded from analysis. BMD at the lumbar spine was correlated with body mass index (BMI) (r=0.278,p=0.0003), age (r=−0.194,p=0.0134) and serum 25OHD (r=0.188,p=0.0167). BMD at the neck of femur correlated with BMI (r=0.391,p<0.0001), age (r=−0.356,p<0.0001), PTH (r=−0.156,p=0.047) and serum 25OHD (r=0.231,p=0.0031). Stepwise multiple regression analysis showed that age, BMI and serum 25OHD contributed to the variation in BMD at lumbar spine. At the neck of femur, PTH was an additional contributor. We conclude that serum 25OHD makes a contribution to BMD a lumbar spine and neck of femur.     

Treatment of Glucocorticoid-Induced Osteoporosis with Alfacalcidol/Calcium Versus Vitamin D/Calcium

Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1α) compared with the native vitamin D₃ in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 μg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D₃ plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score −3.28 and −3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1α (+2.0%, P < 0.0001) and no significant changes at the femoral neck. In the D₃ group, there were no significant changes at both sites. At the end of the study, 12 new vertebral fractures had occurred in 10 patients of the group 1α and 21 in 17 patients of the D₃ group. In accordance with the observed fracture rates, the alfacalcidol group showed a significant decrease in back pain (P < 0.0001) whereas no change was seen in the vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.     

High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency

ObjectivesRecent large trials indicate that adherence associated with a daily regimen of vitamin D is low and limits anti-fracture efficacy with vitamin D supplementation. The aim of this report is to describe changes of 25-hydroxyvitamin D (25(OH)D) serum concentrations achieved with a single oral dose of 300 000 IU vitamin D3.MethodsOver a course of 4 months, we identified 33 elderly with severe vitamin D deficiency (25(OH)D < 25 nmol/l) on admission to acute care. Patients were admitted for musculoskeletal pain, bone disease, or gait abnormalities. The mean age was 80.5 years (SD ± 6.1). All patients were treated with a single oral dose of 300 000 IU D3 in combination with 500–1000 mg calcium supplements per day depending on their dietary calcium intake.ResultsBaseline mean 25(OH)D serum concentrations were 15 nmol/l (SD ± 5.5). Mean 25(OH)D serum concentrations increased to 81.4 nmol/l (SD ± 29.7) at 3 months (29 patients) and were still 69.0 nmol/l (SD ± 17.9) at 6 months (26 patients). Mean serum calcium levels were 2.24 mmol/l (SD ± 0.11) at baseline, 2.28 mmol/l (SD ± 0.18) at 3 months, and 2.28 mmol/l (SD ± 0.13) at 6 months. Two patients with mild hypercalcemia (2.69 mmol/l) at 3 months had normal values at 6 months.ConclusionBased on our observations, a single oral dose of 300 000 IU vitamin D3 raises mean 25(OH)D serum concentrations to the target mean of above 75 nmol/l at 3 months and a mean level of 69 nmol/l at 6 months. As calcium absorption is enhanced with higher 25(OH)D serum concentrations, calcium supplementation may need downward adjustment with this regimen to avoid mild hypercalcemia.     

二膦酸盐联合维生素D治疗糖皮质激素性骨质疏松和骨量减少的初步观察

目的：观察联合维生素D和第三代二膦酸盐对糖皮质激素长期应用所造成的骨量丢失肾炎患者的疗效。方法：15例来自本院经定量CT（QCT）诊断为糖皮质激素性骨质疏松和骨量减少病情稳定肾炎患者,服用钙尔奇1片/d和福善美70mg/周,观察入选时及治疗6月后临床症状和空腹血钙、磷、甲状旁腺激素、碱性磷酸酶、24h尿钙、磷和定量CT腰椎骨密度值变化。结果：疼痛症状改善总有效率（显效加有效）为53.3%。治疗6个月前后血钙、磷、甲状旁腺激素、碱性磷酸酶、24h尿钙、磷变化,无统计学意义（P〉0.05）,腰椎骨密度差值为（11.8±5.3）mg/cm^3,经检验有统计学意义（P〈0.01）。结论：维生素D联合二膦酸盐能有效改善糖皮质激素长期应用所造成的骨量丢失,增加骨密度,改善疼痛,有利于最大程度的预防骨质疏松骨折,但是否优于传统单纯钙和维生素D治疗有待进一步对照研究。     

Vitamin D supplements in chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a significant public health problem and Vitamin D deficiency is prevalent in CKD and might be associated with calcium and phosphate metabolism, cardiovascular disease, infections as well as the progress of kidney dysfunction. Emerging evidence implies that Vitamin D supplements may be of benefit to CKD. Based on existing laboratory and clinical evidence, this review intends to discuss the effectiveness of Vitamin D supplements and controversy in clinical practice. The effect of Vitamin D in CKD patients is summarized in detail from CKD–mineral bone disease, the progression of renal function, cardiovascular events and immune system. Considerable disputes exist for the Vitamin D supplements in CKD, and a growing amount of experimental evidence and some clinical evidence are now gathering from in vitro, animal and epidemiological studies.     

Vitamin D status and response to treatment in post-menopausal osteoporosis

Summary  Treatment with anti-resorptive agents over 13 months was associated with for three to fivefold lower bone mineral density changes and 1.5-fold increased risk of incidence fracture in vitamin D insufficient as compared to vitamin D repleted postmenopausal osteoporotic women. Introduction  Several drugs were registered for the treatment of osteoporosis on the basis of clinical trials in which vitamin D repletion was a pre-requisite inclusion criteria and vitamin D supplements were used as adjunctive therapy. However, in routine clinical practice these supplements are not consistently recommended. Methods  We studied 1515 women with postmenopausal osteoporosis under treatment with anti-resorbing agents (alendronate, risedronate, raloxifene) for 13.1 months with an adherence > 75%. The patients were classified as vitamin D deficient (N = 514) or vitamin D repleted (N = 1001) according to risk factors (N = 1062) or the level of 25(OH) vitamin D [25(OH)D] above or below 50 nmol/l (N = 453). Results  Vitamin D deficient and vitamin D repleted subjects differed significantly for annualized spine and hip bone mineral density (BMD) changes adjusted for all available confounding factors (type of treatment, age, global calcium intake, baseline BMD values). One hundred fifty one patients suffered from a new incident clinical fracture. The adjusted odds ratio for incident fractures in vitamin D deficient as compared to vitamin D repleted women was 1.77 (1.20 – 2.59, 95% CI; p = 0.004). Conclusions  Optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy.     

Wintertime Vitamin D Deficiency in Male Adolescents: Effect on Parathyroid Function and Response to Vitamin D3 Supplements

The first part of this study consisted of an 18 month follow-up of the vitamin D status and parathyroid function in a group of 54 French male adolescents, aged from 13 to 16 years old and all pupils of a jockey training school. During the 18 month period four samplings were made, one every 6 months. The first was during September of the first year, the second and third during March and October of the second year, and the last in March of the third year. Therefore we had two main periods: summer and winter. The summer 25-hydroxyvitamin D (25(OH)D) concentrations were higher (71.6 ± 19.9 and 52.4 ± 16.5 nmol/l) than the winter ones (20.4 ± 6.9 and 21.4 ± 6.1 nmol/l). Conversely, the winter intact parathyroid hormone (iPTH) serum levels (4.18 ± 1.18 and 4.11 ± 1.35 pmol/l) were higher than the summer ones (2.44 ± 0.82 and 2.71 ± 0.71 pmol/l). At the two winter time points the 25(OH)D concentrations were lower than 25 nmol/l (10 ng/ml) in 72% (2nd year) and 68% (3rd year) of the adolescents. In the second part of the study we tried a vitamin D₃ supplementation procedure designed to maintain the 25(OH)D and iPTH postsummer serum levels throughout the winter. Pairs of male adolescents matched for height, weight and Tanner pubertal stage were randomly assigned to either vitamin D₃ supplementation (2.5 mg, i.e., 100 000 IU) administered orally at three specific periods (end of September, November and January) or no vitamin D₃ treatment (control subjects). Blood was collected just before the first intake of vitamin D₃ and 2 months after the last intake (March). The control subjects had blood drawn at the same time points. In the vitamin D₃-treated subjects, the concentrations of 25 (OH)D (55.3 ± 11.5 nmol/l) and of iPTH (3.09 ± 1.16 pmol/l) in March and September (53.8 ± 12.3 nmol/l and 2.75 ± 1.26 pmol/l) were not significantly different. In the control subjects, March 25(OH)D levels (21.0 ± nmol/l were low, with values below 25 nmol/l in 78% of subjects, and iPTH concentrations (3.97 ± 1.08 pmol/l) were significantly (p<0.001) higher than in September (2.91 ± 0.81 pmol/l). The constant vitamin D wintertime deficiency and wintertime rise in iPTH in adolescent French males throughout puberty has been demonstrated. In adolescents with low dairy calcium intakes, the vitamin D₃ treatment was sufficient to maintain 25(OH)D concentrations at their summer levels throughout winter and to prevent an excessive wintertime rise in iPTH levels. Received: 6 February 2001 / Accepted: 9 May 2001     

维生素D研究的新趋势——维生素D免疫学

本文作者概述了维生素D免疫学的三个发展阶段。发现免疫细胞存在维生素D受体和活化的巨噬细胞可以将25(OH)D，羟化为1，25(OH)2D3；在整体动物身上证明维生素D缺乏和药理剂量的维生素D激素抑制T细胞调节免疫；用维生素D激素预防和治疗自身免疫性疾病和抑制器官移植排斥反应。本文作者特别介绍了维生素D激素及其类似物在预防和治疗实验性自身免疫性脑脊髓炎(EAE)，胰岛素依赖性糖尿病(IDDM)和类风湿性关节炎(RA)等自身免疫性疾病和抑制器官移植排斥反应方面的进展，以及1，25(OH)2D3对细胞因子生成的调控。最后简述了自身免疫性疾病光免疫流行病学的启示。