Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women

Summary We studied 20 healthy premenopausal women aged 36.5±4.0 years (mean±1 SD), 123 healthy postmenopausal women aged 50.0±2.4 years, and 103 postmenopausal women aged 65.1±5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)₂D₃, and 1,25(OH)₂D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protien), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)₂D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women, serum 1,25(OH)₂D was related to forearm bone mass (r=−0.20;P<0.05), intestinal calcium absorption (r=0.18;P<0.05), and 24-hour urinary calcium (r=0.21;P<0.05); serum 25(OH)D was related to spinal bone mass (r=0.23;P<0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)₂D was related to bone Gla protein (r=0.33;P<0.001), serum phosphate (r=−0.27;P<0.01), and 24-hour urinary calcium (r=0.43;P<0.001). The present study demonstrates that in a population that is apparently not deficient in vitamin D, a disturbance of the vitamin D metabolism is not likely to play a pathogenetic role in early postmenopausal bone loss. Patients with spinal fractures have low levels of vitamin D metabolites, which may aggravate their osteoporosis.     

Relationship between age,renal function and bone mineral density in the US population

Bisphosphonate drugs for treating osteoporosis are excreted by the kidney. However, many of the major trials on efficacy and safety of the bisphophonates for treating osteoporosis excluded patients with significant renal compromise. Since both osteoporosis and renal insufficiency become more prevalent with age, it seems prudent for physicians to be aware of the prevalence of renal dysfunction in patients with osteoporosis who are candidates for treatment with bisphosphonates. Data on 13,831 men and women aged 20+ from the Third National Health and Nutrition Examination Survey, 1988–1994 (NHANES III) were used to study the occurrence of compromise in renal clearance function in men and women with osteopenia and osteoporosis. To estimate creatinine clearance (CCr), a measure of renal function, serum creatinine (sCr), weight and age were inserted into the Cockcoft-Gault (C-G) formula. The World Health Organization gender specific bone mineral density (BMD) cut-offs were used to define the populations with osteopenia and osteoporosis. For women ages 20–80+ with osteoporosis, the percent prevalence (95% CI) for mild to moderate compromise of CCr 60 ml/min is estimated to be 85% (79%, 91%) and for severe renal compromise of CCr <35 ml/min to be 24% (19%, 29%). In women with osteoporosis and severe compromise, the age specific prevalence is negligible through ages 50–59 and then rises steeply to 54% (46%, 62%) for ages 80+. Similarly, in women with osteopenia and severe renal compromise, the age specific prevalence is also negligible through ages 50–59 and then rises to 37% (28%, 45%) for ages 80+. Lower prevalence estimates hold for men with about 11% of men with osteoporosis having severe renal compromise as compared to 24% for women. These data suggest that there is a substantial prevalence of candidates for treatment of osteoporosis and osteopenia who have significant renal compromise but for whom there is a dearth of clinical trial data on the impact of treatment.     

胰岛素抵抗在2型糖尿病时血清维生素 D3和骨密度变化中的意义

目的检测胰岛素抵抗(IR)和2型糖尿病(T2DM)大鼠的胰岛鼠抵抗情况、血清25-(OH)D3和1,25-(OH)2D3水平、腰椎和股骨骨密度(BMD),探讨IR与2型糖尿病时血清维生素D3和骨密度变化中的意义。方法 18月龄wistar大鼠30只,分为正常对照组(N组)、胰岛素抵抗组(I组)、糖尿病组(D组),正常血糖胰岛素钳夹技术(EICT)测定各组大鼠IR,葡萄糖输注速率(GIR)表示IR,放免法测定各组大鼠血25-(OH)D3和1,25-(OH)2D3水平,双能X线骨密度测量仪(DEXA)测定各组大鼠腰椎、股骨BMD。结果 D组和I组GIR相当,均显著低于N组(P0.01),I组1,25-(OH)2D3低于N组(P0.05),高于D组(P0.01),三组间25-(OH)D3无显著差异,I组腰椎、股骨BMD低于N照组,高于D组(P0.05)。结论 IR是2型糖尿病导致血清活性维生素D3降低和骨密度下降的重要病理生理基础。     

Effect of aging on vitamin D stores and bone density in women

Summary It has been suggested that the decrease in vitamin D stores with aging is a contributory cause of age-related osteoporosis. We studied this question by measuring bone mineral density (BMD) of the mid-radius, distal radius, and lumbar spine assessed by single and dual photon absorptiometry in 122 women, aged 33–94 years, selected from a random sample of Rochester, MN residents. We measured serum 25-hydroxyvitamin D (25OHD), the major storage from of vitamin D, as well as 25OHD₃ (representing both endogenous and exogenous sources of vitamin D), and 25OHD₂, (representing only exogenous sources). Both baseline serum total 25OHD (r=−0.29,P<0.001) and the metabolite 25OHD₃ (r=−0.41,P<0.001), were negatively associated with age at baseline. After adjusting for the effect of age by multiple regression analysis, there was no association between serum levels of 25OHD₂, 25OHD₃, or total 25OHD and BMD for any of the three skeletal scanning sites. Thus, in a northern American population we cannot demonstrate that reduced bioavailability of vitamin D plays a major role in age-related bone loss.     

The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D

Summary To test the hypothesis that estrogen modulates the metabolism of 25-hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvitamin D (1,25(OH)₂D) and 24, 25-dihydroxyvitamin D (24, 25(OH)₂D), we studied 20 normal premenopausal women at four consecutive weekly intervals during one menstrual cycle. Estrogen stimulation was semiquantitatively defined into baseline, lowgrade, or medium-grade categories, based on endogenous estrone and estradiol concentrations. 1,25(OH)₂D increased incrementally from baseline levels of 34±3(SE) pg/ml to 39±3 pg/ml (P=0.2) with low-grade estrogen stimulation and to 43±3 pg/ml (P<0.05) with medium-grade estrogen stimulation, while 25(OH)D, 24,25(OH)₂D, vitamin D binding protein, parathyroid hormone, calcium, and phosphate did not change. 24,25(OH)₂D was correlated to 25(OH)D at baseline (r=0.65,P<0.01) and with low-grade estrogen stimulation (r=0.062,P<0.01), but not with medium-grade stimulation (r=0.13); these relationships are consistent with the concepts that 25(OH)D is metabolized predominantly to 24,25(OH)₂D at low estrogen levels, but not at higher estrogen levels. We conclude that endogenous estrogen elevation promotes formation of 1,25(OH)₂D from 25(OH)D, and that it may reciprocally inhibit synthesis of 24,25(OH)₂D.     

1,25(OH)2D and 24,25(OH)2D production in the developing kidney

To clarify the state of vitamin D production by the developing kidney, firstly, we measured serum levels of 1,25(OH)₂D and 24,25(OH)₂D in humans of different ages (pregnant and nonpregnant women, adult males, children and newborn infants) and secondly, we measured 1- and 24-hydroxylase activity in the kidney mitochrondria of rats at different ages. The mean serum levels of 1,25(OH)₂D in pregnant women, cord blood and newborns were significantly higher than those in children and non-pregnant women and adult males. In newborns, the level increased with gestational age. Synthesis of 1,25(OH)₂D was, at least in part, under the control of the fetus and newborn, rather then being solely a reflection of the conditions prevailing in the mother. The 1-hydroxylase activity in mitochondria was highest in the 1- to 2-month-old rats, and it decreased gradually thereafter. The change in 1-hydroxylase activity with age was due to a change in the V_max of the system.     

Actions of parathyroid hormone and 1,25-dihydroxycholecalciferol on citrate decarboxylation in osteoblast-like bone cells differ in calcium requirement and in sensitivity to trifluoperazine

Summary The actions of PTH in OB bone cells appear to involve both calcium and cAMP. At present little information exists regarding the relationship, if any, between these two putative second messengers of hormone action in bone cells. In this report the molecular role of calcium in the actions of PTH and 1,25(OH)₂D₃ has been compared, since like PTH, the steroid 1,25(OH)₂D₃ is a potent bone resorbing hormone that exerts inhibition of citrate decarboxylation in OB cells, but unlike PTH does not activate adenylate cyclase. It was found that 1,25(OH)₂D₃ could initiate near maximum inhibition of citrate decarboxylation at extracellular calcium levels as low as 0.05 mM, whereas PTH effects began to be apparent only at 0.1 mM calcium, and maximum inhibition of citrate decarboxylation by PTH required 0.5 mM Ca. In addition, PTH-induced decrease in citrate decarboxylation was inhibited by low doses of TFP, an inhibitor of calmodulin and calcium-dependent, phospholipid-sensitive protein kinases, in contrast to 1,25(OH)₂D₃, whose effects were not reduced by this agent. These results suggest that: (a) the actions of 1,25(OH)₂D₃ may not be directly dependent on calcium influx; (b) in OB cell response to PTH a relationship probably exists between cAMP and calcium; and (c) this relationship may involve calmodulin, or calcium-dependent protein kinases that can be inhibited by TFP.     

Oral 1,25-dihydroxyvitamin D3 loading test in normal subjects and patients with chronic renal failure under haemodialysis

Summary: The present study was designed to determine the criterion for 1,25-dihydroxyvitamin D₃ (1,25 (OH)₂D₃) loading test in normal subjects and haemodialysis patients. Fourteen normal subjects were administered 1.0 μg of 1,25(OH)₂D₃ per os and serum 1,25(OH)₂D was monitored every hour up to 6 h afterwards under conditions of overnight fasting, and six haemodialysis patients were administered 2.0 μg of 1,25(OH)₂D₃ per os and serum 1,25(OH)₂D was monitored every 2 h up to 12 h afterwards. Peak time of serum 1,25 (OH)₂D varied between 2 and 5 h after administration in normal subjects. However, there was a good correlation between the maximum increment of 1,25(OH)₂D (maxΔ1,25(OH)₂D) and the increment at 4 h after administration (Δ1,25(OH)₂D(4 h)). the peak time of Δ1,25(OH)₂D in six haemodialysis patients was also at 4 h after administration. From these observations, Δ1,25(OH)₂D(4 h) was evaluated in subsequent studies. Twenty-six normal subjects and 24 haemodialysis patients were administered 0.5–2.0 μg of 1,25(OH)₂D₃ per os, according to their bodyweights, under conditions of overnight fasting. Blood samples were drawn for measuring 1,25(OH)₂D prior to and 4 h after administration. Δ1,25(OH)₂D(4 h) showed good correlation with the dose of 1, 25 (OH)2D3 adjusted by bodyweight (ng/kg bodyweight). the ratio of Δ1,25(OH)₂D(4 h) and adjusted dose of 1,25(OH)₂D₃ was more than 2.0 in all normal subjects (range: 1.97?2.89, mean ± SD: 2.38 ± 0.287). Moreover, the ratio of Δ1,25(OH)₂D(4 h) and adjusted dose of 1,25(OH)₂D₃ showed a good reproducibility (CV%= 5.7 Δ 0.32, n=5), and did not depend on the administered dose of 1,25(OH)₂D₃, suggesting that this ratio is a good parameter for the intestinal absorption of 1,25(OH)₂D₃. In haemodialysis patients, the mean ratio of Δ1,25 (OH)₂D(4 h) and adjusted dose of 1,25(OH)₂D₃ was 2.14 Δ 0.489, which was not significantly different from the ratio in normal subjects, suggesting that, fundamentally, there was no impairment of intestinal absorption of 1,25(OH)₂D₃ in these patients. However, low ratios of Δ(4 h) and the dose of 1,25(OH)₂D₃ with low basal levels of 1,25(OH)₂D were observed in some patients (less than 1.5 in four patients), suggesting that there exist haemodialysis patients with malabsorption of 1,25(OH)₂D₃. From these results, the criterion for normal response in 1,25(OH)₂D loading test was proposed, namely, that the ratio of Δ1,25(OH)₂D(4 h) and adjusted dose of 1,25(OH)₂D₃ be more than 2.0.     

Effects of vitamin D-binding protein on bone resorption stimulated by 1,25 dihydroxyvitamin D3

Summary Vitamin D and its metabolites are tightly bound to the serum vitamin D-binding protein (DBP) and only the free hormone is considered to be physiologically active. On the other hand, DBP could interact with cell membranes and even favor its intracellular entry. The present study was undertaken to examine the effects of DBP on bone resorption stimulated by 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃]. Forelimb bones from 19-day-old fetal rats were cultured for 5 days in the presence of purified human or rat serum albumin (hSAP or rSAP) and 1,25(OH)₂D₃, with or without human or rat DBP (hDBP or rDBP). Bone resorption was assessed by measuring the release of previously incorporated⁴⁵Ca. We found that the resorptive response to 1,25(OH)₂D₃ was minimally altered by hDBP (5 μM). The minimal effects of hDBP on 1,25(OH)₂D₃ activity on rat bones might be explained by a 6-fold lower affinity of hDBP (1.1×10⁷ M⁻¹) than rDBP (5.9×10⁷ M⁻¹) for 1,25(OH)₂D₃ or by species differences in cellular recognition of DBP. In a homologous rat system, however, rDBP at low (0.5 μM) or physiological (5 μM) concentration significantly decreased 1,25(OH)₂D₃-induced bone resorption. These data therefore support the hypothesis that free rather than DBP-bound 1,25(OH)₂D₃ is physiologically important.     

维生素D受体在骨动态平衡中的调节作用

维生素D受体（ vitamin D receptor, VDR）是调控骨发育、代谢和动态平衡的重要分子,其作用机制涉及遗传基因、信号通路、激素及旁分泌因子等多方面,而VDR信号通路则在其中起到重要的调控作用。虽然针对VDR研制的药物已对骨质疏松疾病的治疗表现出较好效果,但近年来研究发现,通过饮食调节钙和磷的摄取可以纠正VDR缺陷小鼠的骨质损伤表现,该发现对VDR在正常生理状态下骨动态平衡以及骨代谢中的重要性提出了异议。最近有研究提出,VDR的表达主要存在于松质骨未成熟成骨细胞,在其他骨细胞中的表达和功能有待进一步验证。因此,VDR在不同类型骨细胞中的表达及其在骨动态平衡中的作用机制还有待更进一步的研究,有关机理的阐明将为我们深入了解骨质疏松的发病机制奠定基础,从而指导临床相关疾病的治疗。     

1,25-dihydroxyvitamin D3 causes an increase in the number of osteoclastlike cells in cat bone marrow cultures

Summary The direct effect of 1,25(OH)₂D₃ upon osteoclast formation from precursor cells is still unknown. In the present experiments we have tested the effects of 1,25(OH)₂D₃ on the generation of osteoclastlike cells in cat bone marrow cultures. These cultures contain proliferating nonattached mononuclear cells and precursor cells that subsequently attach to the culture flask surface and then fuse to form multinucleated osteoclastlike cells. After 7 days of culture we separated the nonattached precursor cells from the attached cells and studied the effects of 1,25(OH)₂D₃ (10⁻¹⁰ M–10⁻⁸ M) on multinucleated cell formation in these two cell populations. In cultures derived from the non-attached precursor cells, 7 days of treatment with 1,25(OH)₂D₃ (10⁻⁸ M) resulted in a 180% increase in the number of attached mononuclear cells and a 90% increase in the number of nuclei contained within multinucleated cells. These effects were dose-dependent. 1,25(OH)₂D₃ did not have a consistent effect on the number of nonattached precursor cells. In cultures derived from attached cells, 7 days of treatment with 1,25(OH)₂D₃ (10⁻⁸ M) induced a 50% increase in the number of mononuclear attached cells and a 40% increase in the number of nuclei within polykaryons. The most likely explanation for these results is that 1,25(OH)₂D₃ promotes the differentiation and subsequent adhesion of nonattached precursor cells, stimulates proliferation of attached mononuclear precursor cells, and possibly stimulates fusion of these attached precursor cells.     

The calciuria of increased fixed acid production in humans: Evidence against a role for parathyroid hormone and 1,25(OH)2-vitamin D

Summary We measured mineral and acid balances, serum iPTH, urinary cAMP/creatinine, and plasma concentrations of 25OHD and 1,25(OH)₂D in 7 healthy adults during control conditions and during increased fixed acid production achieved either by the administration of NH₄Cl (N=3) or by increased dietary protein intake (N=4). When acid production was increased, the subjects were in positive acid balance and negative Ca balance because of increased urinary Ca excretion. Serum iPTH fell slightly but urinary cAMP and the plasma levels of vitamin D metabolites did not change. We conclude that the accelerated skeletal and urinary losses of Ca that occur when fixed acid production is increased are not contributed to nor compensated for by the parathyroid-vitamin D endocrine systems.     

Inhibition by aminohydroxypropylidene bisphosphonate (AHPrBP) of 1,25(OH)2 vitamin D3-induced stimulated bone turnover in the mouse

Summary The purpose of this study was to evaluate whether the 1,25(OH)₂D₃-induced increased bone mineralization in the mouse occurs in response to stimulation of bone resorption. In order to inhibit bone resorption, 35-day-old mice were given 16 μmol/kg/day of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (AHPrBP) for 10 days, the first injection occurring 3 days prior to the continuous infusion of 0.06, 0.13, or 0.20 μg/kg/day of 1,25(OH)₂D₃ for 7 days. Two groups of mice were treated with AHPrBP or 1,25(OH)₂D₃ alone. The skeletal changes were assessed by histomorphometric study of caudal vertebrae after double³H-proline and double tetracycline labelings for evaluation of the matrix apposition rate (MaAR) and mineral apposition rate (MiAR), respectively. Treatment with AHPrBP alone or combined to 1,25(OH)₂D₃ decreased the number of acid phosphatase-stained osteoclasts and reduced the endosteal MaAR and MiAR and the amount of osteoid. When given alone, 1,25(OH)₂D₃ increased serum calcium above normal, enhanced the number of histochemically active osteoclasts, and stimulated the endosteal MiAR. Pretreatment with AHPrBP blocked both the increase in serum calcium and the stimulation of the MiAR induced by 1,25(OH)₂D₃ infusion though serum 1,25(OH)₂D₃ levels rose according to the dose given. The results show that 1) the serum calcium and the bone resorbing responses to 1,25(OH)₂D₃ infusion are prevented by pretreatment with AHPrBP, and 2) the stimulatory effect of 1,25(OH)₂D₃ on the mineralization rate is blocked when bone resorption is inhibited. The data indicate that 1,25(OH)₂D₃ promotes bone mineralization in the mouse mainly in response to stimulation of bone resorption.     

1,25 dihydroxyvitamin D3 alone or in combination with parathyroid hormone does not increase bone mass in young rats

Summary Parathyroid hormone (PTH) alone is known to increase bone mass, but clinical studies of osteoporotic men suggest that when 1,25 dihydroxyvitamin D₃ (1,25(OH)₂D₃) is given in combination with PTH, the effect on bone growth is enhanced. To determine if 1,25(OH)₂D₃ alone would stimulate bone growth, young male rats were given daily subcutaneous injections of either vehicle or 2.5, 5, 10, or 20 ng 1,25(OH)₂D₃ per 100 g body weight for 30 days. To determine if 1,25(OH)₂D₃ would augment the PTH anabolic response, rats were given daily subcutaneous injections of either vehicle for 12 days; or 4 μg/100 g hPTH alone or in combination with 5 ng/100 g 1,25(OH)₂D₃; or 8 μg/100 g hPTH alone or in combination with 5 ng/100 g 1,25(OH)₂D₃. Calcium (Ca), dry weight (DW), and hydroxyproline (Hyp) of the distal femur; the rate of mineralization in the metaphysis of the proximal tibia; and serum calcium and phosphate were measured. Low normocalcemic doses of 1,25(OH)₂D₃ did not significantly stimulate bone growth. 1,25(OH)₂D₃ did not augment the PTH-stimulated anabolic effect in young male rats. Low doses (2.5 and 5 ng) of 1,25(OH)₂D₃ were not hypercalcemic, and there was no increase in total bone calcium or dry weight although the 5 ng dose increased trabecular bone calcium. 1,25(OH)₂D₃ at 10 and 20 ng increased trabecular bone DW and Hyp, but mineralization was impaired and rats were hypercalcemic. 1,25(OH)₂D₃ in combination with PTH did not augment the PTH stimulation of bone growth as trabecular and cortical bone Ca, DW, and HYP were not increased in rats given both hPTH and 1,25(OH)₂D₃ compared with values for rats treated with hPTH alone.     

Effects of phosphate and 1,25(OH)2D3 on in vitro bone collagen synthesis in the hypophosphatemic mouse

Summary Calvarial bones from hypophosphatemic (Hyp) mice and normal littermates were cultured in a chemically defined medium to determine: (a) the effect of medium phosphate (Pi) concentration (1, 2, and 3 mM) on collagen synthesis; (b) the effect of 1,25-dihydroxycholecalciferol [1,25(OH)₂D₃] (10⁻¹²M–10⁻⁷M) on collagen synthesis; and (c) whether bone responsiveness to 1,25(OH)₂D₃ was affected by changes in medium Pi concentration. Bone collagen synthesis was evaluated by measuring [³H]hydroxyproline formation. The distribution of labeled hydroxyproline between bone explant and culture medium (total and dialyzable fraction) was studied. These experiments confirm that 1,25(OH)₂D₃ inhibits specifically bone collagen synthesis in vitro. We did not detect any effect of medium Pi concentration on basal collagen synthesis but were able to demonstrate that lowering medium Pi concentration increased the 1,25(OH)₂D₃-induced inhibition of collagen synthesis. Bones from both genotypes responded to 1,25(OH)₂D₃, but modulation of this response by changes in Pi concentration was altered in Hyp bone as, in contrast to normal bone, its response to 1,25(OH)₂D₃ was unaffected when medium Pi concentration was decreased from 3 to 2 mM. These findings support the hypothesis of an altered response of bone to 1,25(OH)₂D₃ in the Hyp mouse.     

Hypercalcemia associated with increased circulating 1,25 dihydroxyvitamin D in a patient with pulmonary tuberculosis

Summary Studies are described in a 53-year-old man with far-advanced pulmonary tuberculosis who developed transient increases in circulating 1,25 dihydroxyvitamin D (1,25(OH)₂D) and hypercalcemia while on antituberculous treatment. Serial dilution of an extract of the patient's serum obtained while he was hypercalcemic displaced [³H]-1,25(OH)₂D₃ from chick intestinal receptor in a manner identical to authentic 1,25(OH)₂D₃. Serum 25-hydroxyvitamin D (25OHD) was suppressed during the abnormal elevation of serum 1,25(OH)₂D. It is concluded that tuberculosis is another chronic granulomatous disease in which hypercalcemia may result from abnormal metabolism of vitamin D.     

The influence of dihydroxylated vitamin D metabolites on bone formation in the chick

Summary The ability of 1,25(OH)₂D₃ and of 24,25(OH)₂D₃ to prevent or to heal rickets in chicks was evaluated by studies of plasma biochemistry, growth plate histology, bone morphometry and microradiography, and bone mineralization. 1,25(OH)₂D₃ at a dose of 100 ng/day produced fewest abnormalities compared with vitamin D₃-treated control chicks. Bone growth was slightly greater than vitamin D₃-treated controls in chicks given a lower dose of this metabolite; the reverse was observed in chicks given a higher dose. 24,25(OH)₂D₃ was less effective than 1,25(OH)₂D₃ in preventing rickets even at doses as high as 400 ng/day. Treatment of rachitic chicks with doses of 24,25(OH)₂D₃ up to 300 ng/day produced no healing effect on the bone lesions, in marked contrast to the beneficial effects observed with 1,25(OH)₂D₃.     

Serum calcium regulating hormones in the perinatal period

Summary To clarify perinatal vitamin D metabolism, we measured 25-hydroxyvitamin D (25OHD), 24,25-dihydroxyvitamin D [24,25(OH)₂D], 1,25-dihydroxyvitamin D [1,25(OH)₂D], calcium (Ca), phosphorus (P), parathyroid hormone (PTH), and human calcitonin (CT) in paired maternal, cord, and infant serum. Cord serum 25OHD was significantly lower than the maternal level, and cord serum 24,25(OH)₂D was also significantly below the maternal concentrations. Maternal, cord, and infant serum 1,25(OH)₂D, on the other hand, was significantly higher than the normal adult level. The serum PTH was low, but the CT concentration was high in the cord. Cord serum Ca and P levels were significantly higher than maternal. The reason for the elevated circulating 1,25(OH)₂D level in the perinatal period is uncertain, and we speculate that the possible factors are gonadal steroids, placental lactogen, prolactin, and CT. In addition, serum 24,25(OH)₂D and 1,25(OH)₂D concentrations are under some control by the fetus.     

老龄2型糖尿病大鼠肾1-α羟化酶与骨密度变化的研究

目的 观察老龄2型糖尿病大鼠肾1-α羟化酶改变及其对骨密度的影响。方法 用放免法测定老龄2型糖尿病大鼠（糖尿病组）、维生素功处理的老龄2型糖尿病大鼠（处理1组）、1-α（OH）D3处理的老龄2型糖尿病大鼠（处理2组）和正常老龄大鼠（正常对照组）24h尿白蛋白、血25-（OH）D3和1、25-（OH）2D3水平；用双能X线骨密度测量仪（DEXA）测定各组大鼠腰椎、股骨骨密度。结果 糖尿病组24h尿白蛋白高于其他3组，1、25-（OH）2D3和骨密度低于正常对照组和处理2组。处理1组与糖尿病组比较，25-（OH）D3有升高趋势，1、25-（OH）2D3和骨密度无显著差异。处理2组25-（OH）D3和骨密度低于正常对照组，1、25-（OH）2D3与正常对照组差异不显著。处理1组1、25-（OH）2D3和骨密度较处理2组低，25-（OH）D3较处理2组高。结论 老年2型糖尿病大鼠肾1-α羟化酶活性降低导致血中1、25-（OH）2D3减少和骨密度下降，1-α（OH）D3显著改善这种变化。     

Avian medullary bone in organ culture: Effects of vitamin D metabolites on collagen synthesis

Summary A new organ culture system for the study of bone metabolism has been developed using chicken medullary bone. The presence of viable bone cells in culture was demonstrated by histological and histochemical techniques. Incorporation of³H-proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP) was determined using purified bacterial collagenase. Collagen accounted for approximately 10–15% of the total protein labeled. The addition of 1,25-dihydroxycholecalciferol (1,25 (OH)₂D₃) resulted in a dose-dependent inhibition of³H-proline incorporation into CDP at doses from 10⁻¹⁰M to 10⁻⁷M, with maximal suppression reaching 30% of control. The effect was specific for collagen, since³H-proline incorporation into NCP was unaffected. Hydroxyproline analysis of bone explants and culture medium revealed a 1,25(OH)₂D₃-induced decrease in the³H-hydroxyproline content of the system (bone + medium), suggesting that the effect of 1,25(OH)₂D₃ is due to inhibition of collagen synthesis rather than enhanced collagen degradation, impaiored incorporation of collagen into bone matrix, or bone resorption Medullary bone collagen synthesis was not affected by 24,25(OH)₂D₃, either alone or in combination with 1,25(OH)₂D₃. Structure-activity studies of vitamin D metabolites showed that 1,25(OH)₂D₃ and 1,24,25(OH)₃D₃ were the most potent metabolites tested, followed by 1-alpha(OH)D₃. 25(OH)D₃ and 24,25(OH)₂D₃ had no effect at concentrations as high as 10⁻⁷M. These results indicate a possible role for vitamin D in the regulation of medullary bone formation during the reproductive cycle of the egg-laying hen, and suggest the potential utility of medullary bone as anin vitro model for the study of bone formation