Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid

Carnosic acid, the polyphenolic diterpene derived from rosemary, is a strong dietary antioxidant that exhibits antimutagenic properties in bacteria and anticarcinogenic activity in various cell and animal models. In the present study, we show that carnosic acid (2.5-10 microM) inhibits proliferation of HL-60 and U937 human myeloid leukemia cells (half-maximal inhibitory concentration = 6-7 microM) without induction of apoptotic or necrotic cell death. Growth arrest occurred concomitantly with a transient cell cycle block in the G1 phase, which was accompanied by an increase in the immunodetectable levels of the universal cyclin-dependent kinase inhibitors p21WAFI and p27Kipl. Carnosic acid caused only a marginal induction of differentiation, as monitored by the capacity to generate superoxide radicals and the expression of cell surface antigens (CD11b and CD14) and receptors for the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine. However, at low concentrations, this polyphenol substantially augmented (100- to 1,000-fold) the differentiating effects of 1,25-dihydroxyvitamin D3 and all-trans retinoic acid. Furthermore, such combinations of carnosic acid and any of these differentiation inducers synergistically inhibited proliferation and cell cycle progression. These results indicate that carnosic acid is capable of antiproliferative action in leukemic cells and can cooperate with other natural anticancer compounds in growth-inhibitory and differentiating effects.     

1,25-二羟维生素D3的免疫调节作用

1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3]是维生素D3的活性形式,是第二甾体类激素,它除了调节机体的钙和骨代谢外,还参与免疫系统的分化与调节.1,25-(OH)2D3是通过与它的特定受体--维生素D受体相互作用来实现它的大部分基因效应的,抗原呈递细胞和T细胞是它作用的靶细胞,它的作用主要是诱导产生基因耐受性树突细胞,抑制致病性T淋巴细胞,促进调节性T淋巴细胞的增生.1,25-(OH)2D3及其类似物已经在许多实验模型中被证明能够抑制自身免疫性疾病和移植排斥反应,这是一个复杂和丰富的研究领域,可能让我们发现一种新的治疗自身免疫性疾病和移植排斥反应的重要方法.     

Effects of retinoic acid and 1,25-dihydroxyvitamin D3 on IFN-gamma secretion by mononuclear leukocytes from nulliparous and postparturient dairy cattle

Individual and combined effects of several isomers of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on interferon-gamma (IFN-gamma) secretion by blood mononuclear leukocytes (MNL) from nulliparous and postparturient Holstein cattle were evaluated in vitro. In the first experiment, effects on incubation period (24 to 72 hours) and time of supplementation (0 to 32 hours) with all-trans, 9-cis, 13-cis-, and 9,13-dicis-RAs (0 to 100 nM) on IFN-gamma secretion by pokeweed mitogen (PWM)-stimulated (0 and 10 micrograms/ml) MNL from nulliparous cattle were evaluated. In the second experiment, MNL from postparturient cows (bled at 0, 2, 4, and 16 days postpartum) were stimulated with PWM (0 and 10 micrograms/ml) in the presence of RA isomers (9-cis- or 9,13-dicis-RA; 0 to 100 nM), 1,25-(OH)2D3 (0 to 100 nM), or with combinations of these metabolites. The results show that individual isomers of RA had no effect on IFN-gamma secretion by PWM-stimulated MNL from nulliparous or postparturient cows. Furthermore 1,25-dihydroxyvitamin D3 inhibited IFN-gamma secretion by MNL from nulliparous and postparturient dairy cows; however, the degree of inhibition was greater when 9-cis- and 9,13-dicis-RA were also present in the cultures. Finally mononuclear leukocytes from postparturient dairy cows produced substantially less IFN-gamma than did MNL from nulliparous cattle. It is concluded that retinoic acids individually did not affect the capacity of leukocytes from dairy cattle to secrete IFN-gamma. This result is in marked contrast to studies in monogastric species indicating that RAs inhibit IFN-gamma secretion by peripheral blood T cells. Inhibition of IFN-gamma secretion by 1,25-(OH)2D3 was potentiated by 9-cis- and 9,13-di-cis-retinoics acids, suggesting that an excess of dietary vitamins A and D may compromise further the naturally immunosuppressed postparturient dairy cow. Additional research is necessary to determine if the combined effects of these metabolites on IFN-gamma secretion represent an increased susceptibility of the dairy cow to infectious diseases during the periparturient period. Lower secretion of IFN-gamma by MNL from postpartutient dairy cows, relative to nulliparous cattle, suggests that recently-calved cows are naturally immunosuppressed.     

Enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 deficient mice

To investigate whether impaired osteogenesis resulting from vitamin D deficiency can influence hematopoiesis recovery after radiation, the 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase) gene knockout (KO) mice and wild type (WT) mice were subjected to different doses of gamma ray. The survival rates, peripheral blood cell counts and bone marrow cellularity were studied after irradiation (IR). The survival rates of the KO mice were significantly lower than that of WT mice after 6 or 8 Gy dose of radiation. The recovery of white blood cells in KO mice was significantly delayed compared with that in WT mice after radiation. The red blood cell number in WT mice was observed to increase more than that in KO mice at days 14 and 28 after radiation. The nadir platelet count in KO mice was nearly half of that in WT mice. Dramatically higher bone marrow cell numbers were found in WT mice compared with KO mice. Our findings demonstrate the enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) deficient mice.     

Omega-3 fatty acid supplementation increases 1,25-dihydroxyvitamin D and fetuin-A levels in dialysis patients

Vitamin D deficiency, low levels of fetuin-A, and fibroblast growth factor 23 (FGF-23) are related to vascular calcification, which is associated with cardiovascular disease. We hypothesized that omega-3 fatty acid (FA), which has cardioprotective properties, modifies vitamin D status, fetuin-A, and FGF-23 levels in dialysis patients. In a randomized, open-label, controlled study, a total of 47 patients treated with dialysis for at least 1 year were randomized to treatment for 6 months with omega-3 FAs (Omacor, 3 g/d; Pronova, Sandefjord, Norway) or a control group. Levels of fetuin-A and FGF-23 were measured by enzyme-linked immunoassay, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured by radioimmunoassay. The mean age of the enrolled patients was 57.4 ± 10.4 years, and mean dialysis duration was 46.5 ± 28.1 months. Twenty-seven hemodialysis patients and 16 peritoneal dialysis patients finished this trial. After 6 months, the levels of 1,25-dihydroxyvitamin D and fetuin-A were significantly increased in the group taking the omega-3 FA supplement compared with baseline. Levels of calcium, phosphorous, parathyroid hormone, 25-hydroxyvitamin D, FGF-23, and lipid profiles were not significantly changed in the omega-3 FA–supplemented group after 6 months compared with baseline. The erythrocyte membrane contents of eicosapentaenoic acid and docosahexaenoic acid were significantly increased, and oleic acid content was significantly decreased in the omega-3 FA–supplemented group after 6 months compared with baseline. Regarding vascular calcification and cardiovascular disease, omega-3 FA supplementation may have a clinical benefit caused by activating vitamin D, increasing fetuin-A levels, and modifying erythrocyte membrane FA contents in dialysis patients.     

Lycopene and 1,25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL-60 leukemic cells

Lycopene, the major tomato carotenoid, has been found to inhibit proliferation of several types of cancer cells, including those of breast, lung, and endometrium. By extending the work to the HL-60 promyelocytic leukemia cell line, we aimed to evaluate some mechanistic aspects of this effect. Particularly, the possibility was examined that the antiproliferative action of the carotenoid is associated with induction of cell differentiation. Lycopene treatment resulted in a concentration-dependent reduction in HL-60 cell growth as measured by [3H]thymidine incorporation and cell counting. This effect was accompanied by inhibition of cell cycle progression in the G0/G1 phase as measured by flow cytometry. Lycopene alone induced cell differentiation as measured by phorbol ester-dependent reduction of nitro blue tetrazolium and expression of the cell surface antigen CD14. Results of several recent intervention studies with beta-carotene, which have revealed no beneficial effects of this carotenoid, suggest that a single dietary component cannot explain the anticancer effect of diets rich in vegetables and fruits. Thus another goal of our study was to examine whether lycopene has the ability to synergize with other natural anticancer compounds, such as 1,25-dihydroxyvitamin D3, which when used alone are therapeutically active only at high and toxic concentrations. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibited a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression. Such synergistic antiproliferative and differentiating effects of lycopene and other compounds found in the diet and in plasma may suggest the inclusion of the carotenoid in the diet as a cancer-preventive measure.     

骨化三醇对SD大鼠经链脲佐菌素诱导糖尿病发生过程的影响

目的探讨骨化三醇[1,25（OH）2D3]对链脲佐菌素（streptozocin,STZ）所致SD大鼠糖尿病发生过程的影响,为人类1型糖尿病的预防提供实验依据。方法将28只雄性SD大鼠随机分为3组。20只大鼠采用STZ造成糖尿病模型,其中1,25（OH）2D3组（n=10）造模前4周接受1,25（OH）2D31μg/（kg·d）溶于0.05 ml花生油灌胃,STZ对照组（n=10）造模前4周采用花生油灌胃,0.05ml/d。STZ对照组和1,25（OH）2D3组均于实验第5周开始第1天腹腔注射福氏完全佐剂（CFA）,0.5 ml/只,第2天按30 mg/kg STZ枸椽酸溶液腹腔注射,以STZ对照组全部成模为准,停止造模;成模后2周处死。其余8只为正常对照组,采用花生油灌胃,0.05ml/d,灌胃4周,不注射STZ。观察1,25（OH）2D3对STZ所致SD大鼠糖尿病发病情况及对胰岛素、血糖的影响。结果 STZ对照组10只大鼠全部造模成功,1,25（OH）2D3组10只大鼠中6只成模,造模成功率差异有统计学意义（P〈0.05）。1,25（OH）2D3组血糖曲线下面积（AUC）为（21.301±4.699）mmol·h/L,明显低于STZ对照组[（31.183±4.567）mmol·h/L],差异有统计学意义（P〈0.05）。1,25（OH）2D3组胰岛素AUC为（1.105±0.356）μg·h/L,明显高于STZ对照组[（0.472±0.162）μg·h/L],差异有统计学意义（P〈0.05）。血清1,25（OH）2D3水平与胰岛素AUC呈正相关,而与血糖AUC呈负相关,有统计学意义（r=0.517,P=0.04;r=-0.562,P=0.02）。结论 1,25（OH）2D3对STZ所致SD大鼠糖尿病的发生有一定的预防作用。     

Effect of pyridoxal 5'-phosphate on the 1,25-dihydroxyvitamin D3 receptor system

The effect of pyridoxal 5'-phosphate on the 1,25-dihydroxyvitamin D3 receptor system has been studied by using pig intestinal chromatin. Pyridoxal 5'-phosphate did not affect the binding of 1,25-dihydroxyvitamin D3 to its receptor extracted from chromatin with hypertonic KCl, although in the presence of pyridoxal 5'-phosphate 1,25-dihydroxyvitamin D3-receptor complexes were not readily precipitated with polyethylene glycol. In contrast, pyridoxal 5'-phosphate showed a potency to dissociate the 1,25-dihydroxyvitamin D3 receptor from chromatin in a dose-dependent manner. A low concentration of pyridoxal 5'-phosphate was as effective as hypertonic KCl in dissociating the receptor from chromatin, while pyridoxine, p-nitrophenyl phosphate, or inorganic phosphate was much less effective. These observations suggest the inhibitory effect of pyridoxal 5'-phosphate on the recognition of 1,25-dihydroxyvitamin D3 by its receptor system.     

1,25-二羟基维生素D3对原发性骨质疏松骨代谢的影响

目的探讨1，25-二羟基维生素D3[1，25（OH）2D3]对原发性骨质疏松骨代谢的影响。方法采用8月龄雌性新西兰兔，摘除双侧卵巢建立Ⅰ型骨质疏松模型，随机分为假手术组（Sham）、单纯去卵巢组（OVX）、葡萄糖酸钙组（OC）和葡萄糖酸钙＋1，25（OH）2D，组（OCR）。采用3岁龄新西兰雌兔和4岁龄新西兰雄兔，作为Ⅱ型骨质疏松动物模型，随机分为空白对照组（Control）、葡萄糖酸钙组（Calcium）、葡萄糖酸钙＋1，25（OH）2D3组（CR）。OC组和Calcium组单纯给予葡萄糖酸钙，OCR组和CR组给予葡萄糖酸钙和1，25（OH）2D3。给药8周后测定各实验组的骨代谢生化指标。结果给药8周后，在Ⅰ型骨质疏松模型中，OCR组的血钙、血磷、碱性磷酸酶（ALP）均较OVX组和OC组显著升高（P〈0．05或P〈0．01），OCR组的BGP、尿Ca／Cr较OVX组和OC组明显降低（P〈0．05或P〈0．01）。在Ⅱ型骨质疏松模型中，雌、雄性兔CR组的血钙、BGP、ALP均较Control组和Calcium组有显著性升高（P〈0．05或P〈0．01），尿Ca／Cr较其他两组明显下降（P〈0.05或P〈0．01）。结论1，25（OH）2D3对Ⅰ型骨质疏松症有降低骨转换，促进骨形成，抑制骨吸收的作用；对Ⅱ型骨质疏松症有提高骨转换，促进骨形成，抑制骨吸收的作用。     

1,25-二羟基维生素D3对原发性骨质疏松骨折愈合的影响

目的探讨1，25-二羟基维生素D3（1，25（OH）2D3）对原发性骨质疏松骨折愈合的影响。方法采用8月龄雌性新西兰兔，摘除双侧卵巢法建立Ⅰ型骨质疏松模型，随机分为假手术组（Sham）、单纯去卵巢组（OVX）、葡萄糖酸钙组（OC）和葡萄糖酸钙＋1，25（OH）2D3组（OCR）。采用3岁龄新西兰雌兔和4岁龄新西兰雄兔，作为Ⅱ型骨质疏松动物模型，随机分为空白对照组（Control）、葡萄糖酸钙组（Calcium）、葡萄糖酸钙＋1，25（OH）2D3组（CR）。所有实验动物行双侧桡骨骨折模型。OC组和Calcium组单纯给予葡萄糖酸钙，OCR组和CR组给予葡萄糖酸钙和1，25（OH）2D3。于给药后2、4、8周给各实验组拍骨折X线片，8周测定各实验组骨痂、腰椎的骨密度（BMD），对骨痂组织进行组织学观察。结果给药8周后，OCR组的X线评分、腰椎和骨痂骨密度均较OVX组和OC组显著升高（P〈0.05或P〈0.01）。CR组的X线评分、腰椎和骨痂骨密度均较Control组和Calcium组显著升高（P〈0.05或P〈0.01）。结论1，25（OH）2D3对Ⅰ型和Ⅱ型骨质疏松骨折愈合均有促进作用。     

Gallic acid inhibits cell viability and induces apoptosis in human monocytic cell line U937

In the present study, we investigated the effects of gallic acid (GA) (3,4,5-trihydroxybenzoic acid), a polyhydroxyphenolic compound, isolated from Rhus chinensis, on the human monocytic lymphoma cell line U937. In vitro experiments showed that treating U937 cells with various amounts of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA induces apoptosis, we examined the gene expression of p53, nuclear factor κB (NF-κB), and inhibitor of NF-κB (I-κB) after treating the cells with GA and found that expression levels of the genes for p53 and NF-κB increased and that for I-κB decreased. The results obtained from western blotting with U937 cells showed up-regulation of NF-κB protein and down-regulation of proliferating cell nuclear antigen and I-κB protein. These results demonstrate that GA efficiently induces apoptosis in U937 cells and that GA is a potential chemotherapeutic agent against lymphoma.     

支气管哮喘患者血清1,25-二羟基维生素D3和血管内皮生长因子水平及意义

目的了解支气管哮喘(简称哮喘)患者血清1,25-二羟基维生素D3(1,25(OH)2D3)和血管内皮生长因子(VEGF)水平,比较与正常人的差异。方法纳入2010年7月至12月到我院就诊的62例非稳定期哮喘患者为病例组,同期健康体检者60例为对照组。收集哮喘患者临床信息,并测定所有纳入者血清1,25(OH)2D3、和VEGF水平。结果病例组1,25(OH)2D3水平低于对照组(7.4±3.6vs.28.3±4.1,p<0.01),VEGF明显高于正常对照组(372.3±108.2vs.201.2±77.2,p<0.01),差异有统计学意义。病例组中血清1,25(OH)2D3水平与VEGF水平呈负相关(r=-0.734,p<0.01)。结论支气管哮喘患者血清1,25(OH)2D3和VEGF水平与健康者之间存在差异,这种变化可能与哮喘气道炎症及气道重构有关。     

Changes in serum levels of 1,25-dihydroxyvitamin D3, calcium and phosphorus with age and vitamin D status in chickens

The effects of vitamin D3 (D3) on serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), ionic calcium, total Ca and phosphorus in chicks were studied from the time of hatching until sexual maturity. Chicks fed on a diet low in D3 showed a serum level of 1,25(OH)2D3 higher than that in chicks on a normal-D3 diet, for both sexes and at any given age. A dramatic increase in the serum level of 1,25(OH)2D3 occurred in female birds approaching sexual maturity and in laying hens raised on the low-D3 diet the level was five times that of their counterparts raised on a normal-D3 diet. The serum 1,25(OH)2D3 level in adult males in the low-D3 groups was seven times that of those on the normal-D3 diet. The serum level of 25-hydroxyvitamin D3 remained relatively unchanged at weeks 2 and 15 in birds on a low D3 intake as well as in those fed on a normal-D3 diet. Nevertheless, the levels of 25-hydroxyvitamin D3 were different between the two groups. No significant change was observed in the level of ionized serum Ca in relation to dietary regimen, but there was an increase in total Ca concentration in females with the onset of reproduction. The serum P level decreased gradually with age, reaching a minimum value 3 and 8 weeks before laying commenced in the groups on low- and normal-D3 diets respectively. An increase was observed when the hens began laying.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between 1,25-dihydroxyvitamin D and blood pressure in a geographically defined population

In a cross-sectional, population-based study we measured casual, seated blood pressure with a random-zero sphygmomanometer and 1,25-dihydroxyvitamin D (1,25-[OH]2D) with a protein-binding assay in 373 women aged 20-80 y. 1,25-(OH)2D, an active metabolite that regulates serum calcium, was associated significantly and positively with systolic blood pressure (p = 0.020) and diastolic blood pressure (p = 0.003) after adjustment for age, Quetelet's index (a measure of obesity), and current thiazide use. A model including age, Quetelet's index, current thiazide use, and 1,25-(OH)2D explained 37% of the variability in systolic blood pressure observations, of which 7% of variability was explained by 1,25-(OH)2D. In this geographically defined population of women, the variability of blood-pressure measurements attributable to 1,25-(OH)2D was of the same order of magnitude as that attributable to Quetelet's index.     

25-Hydroxyvitamin D and 1,25-dihydroxyvitamin D of D2 and D3 origin in maternal and umbilical cord serum after vitamin D2 supplementation in human pregnancy

Serum concentrations of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] of vitamin D2 and D3 origin were determined separately in 10 women before vitamin intake in early pregnancy, and repeated in maternal and cord serum obtained at delivery after 20 to 30 wk of vitamin D2 supplementation in a dose of 400 IU/day. Before supplementation 25-OHD2 and 1,25-(OH)D2D2 were present in just traceable or nondetectable concentrations, but the levels increased in all to a mean +/- 1 SD of 7.3 +/- 3.7 ng/ml and 37.2 +/- 18.1 pg/ml, respectively (p less than 0.0025), by the time of delivery. At delivery the total 25-OHD and 1,25-(OH)2D levels were always lower in the cord than in the maternal serum (30.7 +/- 14.2 versus 20.1 +/- 9.1 ng/ml, and 90.1 +/- 31.2 versus 37.3 +/- 11.6 pg/ml, p less than 0.0025). The paired concentrations of 25-OHD were closely related (r = 0.89, p less than 0.0005), while the association for 1,25-(OH)2D was not statistically significant (r = 0.53, p less than .01). The 25-OHD of D2 and D3 origin accounted for a similar proportion of the total 25-OHD in the maternal and cord serum (ratio of 25-OHD2 to 25-OHD3: 0.40 +/- 0.28 versus 0.45 +/- 0.29, p = NS), as did the respective 1,25-(OH)2D metabolites [ratio of 1,25-(OH)2D2 to 1,25-(OH)2D3: 0.73 +/- 0.35 versus 0.90 +/- 0.50, p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum 25-hydroxyvitamin D is a predictor of serum 1,25-dihydroxyvitamin D in overweight and obese patients

Recent research suggests that 1,25-dihydroxyvitamin D [1,25(OH)(2)D], a steroid hormone that regulates calcium homeostasis, may also play a role in the development and progression of cancer, multiple sclerosis, cardiovascular, and other diseases. Decreased serum 1,25(OH)(2)D concentrations are often observed in overweight and obese patients. However, little is known about the factors that may influence 1,25(OH)(2)D renal synthesis, because it is generally accepted that serum 1,25(OH)(2)D concentration is strictly regulated by parathyroid hormone and serum concentrations of calcium and phosphorus. In this study, the associations among serum 1,25(OH)(2)D, serum 25-hydroxyvitamin D [25(OH)D], and body composition were analyzed in 1779 patients with excess body weight registered in a Metabolic and Medical Lifestyle Management Clinic in Oslo, Norway. According to our results, serum 25(OH)D, adiposity, age, season of blood sampling, and gender directly influence serum 1,25(OH)(2)D (r = 0.33; P < 0.001), with serum 25(OH)D being the strongest predictor for serum 1,25(OH)(2)D. The 1,25(OH)(2)D concentrations were 25.4 pmol/L (95% Cl: 19.3-31.5; P < 0.001) lower in the lowest 25(OH)D quartile to compared with highest quartile. A seasonal variation was observed for both vitamin D metabolites. Thus, our results suggest that in patients with excess body weight, serum 1,25(OH)(2)D concentrations were associated with 25(OH)D and varied during the year. Therefore, it may also be valuable to measure both serum 25(OH)D and 1,25(OH)(2)D for the evaluation of vitamin D status in overweight and obese persons.     

Fractures in the men of a Veterans Administration Nursing Home: relation to 1,25-dihydroxyvitamin D.

One hundred fifty-three men, age 48-96, 86% white, had resided in this Nursing Home for an average of 6.3 years (range 1.3-36) as of August 1984. At that time, we reviewed their medical charts to record the numbers and sites of fractures which had been diagnosed during the preceding 1 to 5 years of Nursing Home residence, the duration of this period depending on the duration of institutionalization. In addition, a clinical database was compiled comprising 70 attributes, including diagnoses, drugs, plasma (serum) chemistries, and measures of hematologic, nutritional, and functional status. Fractures during the studied period of Nursing Home residence had occurred in 24 of 153 men; six residents had experienced two or more fractures. Fracture rates in hip, spine, and wrist were 2564, 366, and 549 per 100,000 patient years, respectively. The total fracture rate, hip fracture rate, and limb fracture rate were five to 11 times higher than in the age-matched general population of white men in the United States; in Rochester, MN; in Dundee, England; in Oxford, England; or in Finland. Univariate statistical analysis showed that the rates for hip fracture or for fracture at any site were significantly associated with 13 attributes: directly with age, plasma somatomedin C, blood urea N, serum creatinine, serum uric acid, serum 25-hydroxyvitamin D (25-OH-D), degree of functional impairment, and chronic urinary tract infection, and inversely with serum 1,25-dihydroxyvitamin D [1,25-(OH)2-D], serum albumin, hematocrit, and hemoglobin. There was not a significant correlation with the number of falls/month which occurred during the 7 months after August 1984. After the effect of age was partialed out, somatomedin C, 25-OH-D, 1,25-(OH)2-D, and the diagnosis of urinary tract infection were still significantly related to the occurrence of fractures. The fact that Nursing Home fracture cases had significantly higher blood urea nitrogen and 25-OH-D, and significantly lower 1,25-(OH)2-D, than their non-fracture counterparts suggests that impaired renal production of the latter vitamin D metabolite contributed to the excessive rate of fractures.