Vitamin D therapy in patients with chronic renal disease: the role of the renal dietitian

Chronic renal failure causes decreased vitamin D production, which profoundly alters parathyroid hormone (PTH) metabolism, and calcium and phosphorus balance. Correcting this deficiency is an important strategy in managing secondary hyperparathyroidism (SHPT) and helping to restore mineral balance. However, hypercalcemia and hyperphosphatemia are common side effects that hamper vitamin D hormone therapy by increasing dietary calcium and phosphorus absorption. This limitation has led to the development of D-hormone analogs that retain the ability to suppress PTH levels without causing drastic changes in calcium and phosphorus metabolism. These analogs have the potential to advance the management of SHPT. Renal dietitians can play a leading role in ensuring successful management of SHPT by participating in early patient intervention for abnormal mineral and vitamin D metabolism, by encouraging long-term phosphorus control, and by updating and implementing clinical protocols that promote optimal hormone levels (D and PTH), mineral levels (phosphorus and calcium), and nutritional factors.     

Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients

BACKGROUND: Treatment of secondary hyperparathyroidism (SHPT) includes use of calcitriol (1,25D(3)) to suppress parathyroid hormone (PTH), but dosing of 1,25D(3) is limited by the development of hypercalcemia and a high calcium x phosphorus (Ca x P) product due to gut absorption of calcium and phosphorus as well as enhanced bone resorption. The vitamin D analog 19-Nor-1,25(OH)2-vitamin D2 (paricalcitol) and the prohormone 1alpha-OH-vitamin D2 (doxercalciferol) have been proposed as alternatives which may cause less hypercalcemia and elevated Ca x P, while still suppressing PTH. METHODS: We performed a prospective study to assess the acute bone mobilization effects of very high doses of paricalcitol and doxercalciferol. 13 hemodialysis patients received 160 mcg of paricalcitol and 120 mcg of doxercalciferol on 2 separate occasions in a research center while on a low calcium, low phosphorus diet, and sevelamer alone as a phosphorus binder. Changes in Ca, PO4, and PTH were measured over 36 h. RESULTS: Serum phosphorus rose faster, and peaked significantly higher at 36 h following doxercalciferol (2.12 +/- 0.11 mmol/l) than paricalcitol (1.85 +/- 0.07 mmol/l; p = 0.025). Ca x P product also rose more following doxercalciferol than paricalcitol, and peaked higher at 36 h (5.02 +/- 0.26 vs. 4.54 +/- 0.21 mmol/l; p = 0.061). In contrast, suppression of PTH at 36 h was comparable (63% after paricalcitol and 65% with doxercalciferol). CONCLUSION: Consistent with animal studies, paricalcitol provides profound PTH suppression, while stimulating bone resorption and/or intestinal absorption less than doxercalciferol, resulting in less elevation of serum phosphorus and Ca x P.     

Role of parathyroid hormone and therapy with active vitamin D sterols in renal osteodystrophy

Renal osteodystrophy (ROD) represents a spectrum of bone lesions ranging from a high-turnover to a low-turnover state. The expression of the histologic bone lesions is modulated by parathyroid hormone (PTH), vitamin D, calcium, phosphorus, and aluminum that act as major regulators of osteoblastic activity and bone formation rate. The availability of immunometric PTH assays has allowed reasonable prediction of the subtypes of bone lesions in patients with chronic kidney disease (CKD). PTH levels as measured by these assays, however, may not reflect the true bone turnover state during treatment with intermittent active vitamin D. Early diagnosis and appropriate treatment of renal bone disease are essential in preventing the debilitating consequences of ROD on the growing skeleton. Calcitriol and calcium-containing phosphate binders have been the mainstay of treatment for secondary hyperparathyroidism. Complications such as hypercalcemia, vascular calcifications, and the development of adynamic bone may arise from aggressive treatment. New vitamin D analogs and calcium-free phosphate binders are promising in terms of limiting these complications. The management of ROD should be tailored to maintain normal rates of bone formation and turnover with age-appropriate serum calcium and phosphorus levels and with serum PTH levels that correspond to normal rates of skeletal remodeling. These treatment goals would maintain bone health, maximize growth potential, and prevent the development of soft tissue and vascular calcifications.     

Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D.

Osteoblast activity and plasma 1,25(OH)2 vitamin D are increased in HPT but suppressed in HHM. To model HPT and HHM, we directly compared multiday continuous infusions of PTH versus PTHrP in humans. Continuous infusion of both PTH and PTHrP results in marked and prolonged suppression of bone formation; renal 1,25(OH)2D synthesis was stimulated effectively by PTH but poorly by PTHrP. INTRODUCTION: PTH and PTH-related protein (PTHrP) cause primary hyperparathyroidism (HPT) and humoral hypercalcemia of malignancy (HHM), respectively. Whereas HHM and HPT resemble one another in many respects, osteoblastic bone formation and plasma 1,25(OH)2 vitamin D are increased in HPT but reduced in HHM. MATERIALS AND METHODS: We performed 2- to 4-day continuous infusions of escalating doses of PTH and PTHrP in 61 healthy young adults, comparing the effects on serum calcium and phosphorus, renal calcium and phosphorus handling, 1,25(OH)2 vitamin D, endogenous PTH(1-84) concentrations, and plasma IGF-1 and markers of bone turnover. RESULTS: PTH and PTHrP induced comparable effects on renal calcium and phosphorus handling, and both stimulated IGF-1 and bone resorption similarly. Surprisingly, PTH was consistently more calcemic, reflecting a selectively greater increase in renal 1,25(OH)2 vitamin D production by PTH. Equally surprisingly, continuous infusion of both peptides markedly, continuously, and equivalently suppressed bone formation. CONCLUSIONS: PTHrP and PTH produce markedly different effects on 1,25(OH)2 vitamin D homeostasis in humans, leading to different calcemic responses. Moreover, both peptides produce profound suppression of bone formation over multiple days, contrasting with events in HPT, but mimicking HHM. These findings underscore the facts that the mechanisms underlying the anabolic skeletal response to PTH and PTHrP in humans is poorly understood, as are the signal transduction mechanisms that link the renal PTH receptor to 1,25(OH)2 vitamin D synthesis. These studies emphasize that much remains to be learned regarding the normal regulation of vitamin D metabolism and bone formation in response to PTH and PTHrP in humans.     

The effects of sodium fluoride, calcium phosphate, and vitamin D2 for one to two years on calcium and phosphorus metabolism in postmenopausal women with spinal crush fracture osteoporosis

Calcium and phosphorus balances and 47Ca turnover studies were performed before and after 12-27 months of daily treatment with sodium fluoride (60 mg), calcium (30-45 mmol), phosphate (29-44 mmol), and vitamin D2 (18,000 IU) in 20 postmenopausal women with spinal crush fracture osteoporosis. Before treatment the mean calcium balance (-1.6 mmol Ca/day) was negative (P less than 0.05), whereas the mean phosphorus balance (-1.6 mmol P/day) did not differ from zero (P greater than 0.10). The treatment induced an increase in calcium absorption (P less than 0.01) with an unchanged renal excretion and dermal loss of calcium and an increase (P less than 0.02) in calcium balance, which became positive (P less than 0.01) (+3.3 mmol Ca/day). This enhancement in calcium balance was obtained by the combined effects of an increase (P less than 0.05) in bone mineralization rate and a decrease (P less than 0.05) in bone resorption rate. The observed increase in net phosphorus absorption (P less than 0.001) was more pronounced than the increase in renal excretion of phosphorus (P less than 0.001), and the phosphorus balance therefore increased (P less than 0.001) and became positive (P less than 0.001). A positive correlation was observed between net calcium and net phosphorus absorption (r = 0.065; (P less than 0.001) in the 32 studies where both calcium and phosphorus balance data were available. Furthermore, a positive correlation (r = 0.61; P less than 0.05) was found between the changes in net calcium and net phosphorus absorption during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone mineral content in calcium renal stone formers

Idiopathic renal calcium stone disease often presents with reduced bone mineral content. Investigations using non-invasive methods for the measurement of bone mineral content (single and dual-photon absorptiometry, dual-energy x-ray absorptiometry, quantitative computed tomodensitometry) show a slight decrease in skeletal mineral content of idiopathic renal stone formers (RSFs).The alterations in bone mineral content in RSFs have different explanations: prostaglandin-mediated bone resorption, subtle metabolic acidosis and 1–25 vitamin D disorders. Bone mineral content is worsened by insufficient dietary calcium leading to a negative calcium balance.     

Zinc nutritional status modifies renal osteodystrophy in uremic rats.

BACKGROUND: Previous studies from our laboratories suggested that zinc depletion reduces the circulating level of 1,25-dihydroxycholecalciferol (1,25(OH)2D, calcitriol) in calcium- and phosphorus-depleted rats with normal renal function, and rats with uremia. Since calcitriol synthesis is in part dependent on renal function, we studied levels of circulating vitamin D metabolites, PTH response, mineral balance and bone histomorphometry in animals with different zinc nutritional and renal functional status. METHODS: Fifty-eight male Sprague-Dawley rats were pair-fed zinc-replete (+) or -deplete (-) diets for two weeks. Thereafter, half of each paired group underwent nephrectomy (N), while half had sham (S) operations. Animals were observed for eight weeks after surgery. External mineral balances of zinc, calcium, phosphate and magnesium were determined before surgery, and 1, 2 and 7 weeks after surgery. Plasma creatinine, zinc, calcium, phosphorus, magnesium, 25-hydroxycholecalciferol, calcitriol and PTH were determined at sacrifice. Static and dynamic bone histomorphometry was determined by standard techniques. RESULTS: After an 8-week observation period, zinc-depleted animals had lower plasma zinc levels, and nephrectomized animals had lower creatinine clearances than respective controls at sacrifice. Plasma calcium and phosphorus concentrations were similar in all four groups at sacrifice. Plasma magnesium concentrations were similar in groups with renal insufficiency, regardless of zinc nutritional status. Plasma 25-hydroxycholecalciferol and calcitriol levels were similar in all groups. There was no difference between mean PTH concentration in sham-operated animals, regardless of zinc nutritional status. Although nephrectomized groups' PTH levels were increased compared to S controls, PTH levels were increased in +Zn/N animals compared to the -Zn/N group. Zinc-deplete groups had consistent negative net zinc balance, however, there was no consistent effect of nephrectomy on external calcium, phosphorus, or magnesium balance, when nephrectomized groups of different zinc nutritional status were compared. Nephrectomized animals had histomorphometric changes indicative of higher bone turnover and abnormal mineralization. Zinc deficiency was associated with less evidence of increased parathyroid hormone activity on bone in nephrectomized rats. CONCLUSIONS: Zinc depletion limits the increase in plasma PTH concentration and the expression of secondary hyperparathyroid bone disease during the development of renal insufficiency in the renal ablation model of uremia in rats. The mechanism underlying this effect is unknown, but may involve a direct effect of zinc on the synthesis, release, metabolic clearance, and/or action of PTH on the cellular level, on the interrelationship of calcitriol and PTH, or a direct effect of zinc on bone mineral metabolism. These data highlight the potential relevance of zinc nutritional status to mineral metabolism in patients with chronic renal insufficiency and end-stage renal disease.     

ED-71, a vitamin D analog, is a more potent inhibitor of bone resorption than alfacalcidol in an estrogen-deficient rat model of osteoporosis

Although active vitamin D is used in certain countries for the treatment of osteoporosis, the risk of causing hypercalcemia/hypercalciuria means that there is only a narrow therapeutic window, and this has precluded worldwide approval. The results of our previous animal studies have suggested that the therapeutic effect of active vitamin D on bone loss after estrogen deficiency can be dissociated at least partly from its effect of enhancing intestinal calcium absorption and suppressing parathyroid hormone (PTH) secretion. To test this, we compared the effects of ED-71, a hydroxypropoxy derivative of 1alpha,25-dihydroxyvitamin D3, with orally administered alfacalcidol, on bone mineral density (BMD) and the bone remodeling process as a function of their effects on calcium metabolism and PTH, in a rat ovariectomy (ovx) model of osteoporosis. ED-71 increased bone mass at the lumbar vertebra to a greater extent than alfacalcidol, while enhancing calcium absorption (indicated by urinary calcium excretion) and decreasing serum PTH levels to the same degree as alfacalcidol. ED-71 lowered the biochemical and histological parameters of bone resorption more potently than alfacalcidol, while maintaining bone formation markers. These results suggest that active vitamin D exerts an antiosteoporotic effect by inhibiting osteoclastic bone resorption while maintaining osteoblastic function, and that these anticatabolic/anabolic effects of active vitamin D take place independently of its effects on calcium absorption and PTH. The demonstration that ED-71 is more potent in these properties than alfacalcidol makes it an attractive candidate as an antiosteoporotic drug.     

慢性乙肝性肝硬化症男性患者血清性激素、钙调节激素和骨转换指标的变化

目的　慢性严重肝脏损害常合并肝性骨病。为了探讨终末期肝病患者的钙调节激素变化和骨转换率状态 ,我们回顾性分析了 17例乙肝后肝硬化失代偿的男性患者 ,并和年龄、身高、体重相匹配的健康男性进行对照研究。方法　肝硬化组和对照组均检测其血清性激素 [雄激素 (T)、雌激素 (E2 ) ],钙调节激素 [甲状旁腺素 (PTH)、降钙素 (CT)和 2 5羟维生素D3(2 5 -OHVD3) ]和骨转换指标 [血清骨钙素 (BGP)和尿脱氧吡啶啉 肌酐比值 (Dpd Cr) ]以及钙 (Ca2 + )、磷 (PO3- )和碱性磷酸酶 (ALP)。结果　显示与对照组相比 ,肝硬化组血清T明显降低、E2 水平和E2 T比值显著升高 ;血清PTH显著升高、2 5 -OHVD3明显降低 ,而CT差异不大。其中E2 升高和 2 5 -OHVD3降低有极显著意义。肝硬化组血清BGP和Ca2 + 水平明显降低、尿Dpd Cr比值和尿Ca2 + Cr比值明显升高。而血清CT和PO3- 差异不大。结论　我们认为慢性严重肝硬化患者骨量减低 ,呈现出骨形成降低、骨吸收增强之特征 ,与维生素D和性激素代谢异常有关 ,而PTH升高乃继发性改变     

Bone health and vascular calcification relationships in chronic kidney disease

Abnormal bone in chronic kidney disease (CKD) may adversely affect vascular calcification via disordered calcium and phosphate metabolism. In this context, bone health should be viewed as a prerequisite for the successful prevention/treatment of vascular calcification (VC) along with controlled parathyroid hormone (PTH) secretion, the use of calcium-based phosphate binders and vitamin D therapy. In CKD patients, VC occurs more frequently and progresses more rapidly than in the general population, and is associated with increased cardiovascular disease (CVD) morbidity and mortality. A number of therapies aimed at reducing PTH concentration are associated with an increase of calcaemia and Ca × P product, e.g. calcium-containing phosphate binders or active vitamin D. The introduction of calcium-free phosphate binders has reduced calcium load, attenuating VC and improving trabecular bone content. In addition, a major breakthrough has been achieved through the use of calcimimetics, as first agents which lower PTH without increasing the concentrations of serum calcium and phosphate. Nowadays, it is becoming evident that even early stage CKD is recognised as an independent CVD risk factor. Moreover, the excess of CVD among dialysis patients cannot be explained entirely on the basis of abnormal mineral and bone metabolism. Hence, much controversy has surrounded the cost-effectiveness of treatment with the new phosphate-binding drugs as well as new vitamin D analogs and calcimimetics. Thus, it seems prudent and reasonable that maintaining bone health and mineral homeostasis should rely on some modifications of standard phosphate binding and calcitriol therapy. Hypophosphataemia and hypercalcaemia in adynamic bone disease (ABD) might be treated by reducing the number of calcium carbonate/acetate tablets in order to increase serum phosphate and decrease serum calcium, which, in turn, might positively stimulate PTH secretion. The same rationale is assumed for the use of a low calcium dialysate. On the other hand, secondary hyperparathyroidism with hyperphosphataemia and hypocalcaemia should be treated with a substantial number of calcium carbonate/acetate tablets in combination with calcitriol and low calcium dialysate in order to decrease serum phosphate and maintain the Ca × P product within K/DOQI guidelines (<4.4 mmol l⁻¹). Finally, it becomes apparent that prevention, with judicious use of calcium-based binders, vitamin D and a low calcium dialysate without adverse effects on Ca × P or oversuppression of PTH, provides the best management of VC and mineral and bone disorder in CKD patients.     

Changes in bone mineral in experimentally induced rickets in the rat: Electron microprobe and chemical studies

Summary The elemental composition of trabecular bone was compared for: (a) rats made rachitic on a low phosphorus, vitamin D-deficient diet; (b) rats fed the same diet but supplemented with vitamin D; (c) normal rats fed a standard laboratory diet with normal phosphorus and vitamin D levels. Quantitative energy dispersive X-ray microanalysis was performed on mineralized bone matrix at four sites: (1) clusters of mineral crystals in osteoid; (2) bone matrix adjacent to osteoid containing mineralization clusters; (3) peri-lacunar bone matrix; and (4) deep bone matrix distant from osteocytes. Estimations were also made of serum calcium, phosphorus, and 25-hydroxy-vitamin D, and of calcium, phosphorus, and hydroxyproline in whole bone. At bone sites 2, 3, and 4, the mineral content was greater in the normal group than in the other two groups. At each site, the mineral content of the rachitic bone matrix was greater than that from the vitamin D-treated group. A normal pattern of increasing mineral content with distance into the bone from a recently mineralized border was found in the normal and vitamin D-treated groups but was notably absent in the rachitic bones. Microprobe measurements of Ca:P molar ratios in hydroxyapatite standards and in normal rat bone were approximately 1.7. In both rachitic and vitamin D-treated bones, the Ca:P molar ratio was significantly higher than that in normal bones and correlated with serum Ca:P ratios. It is suggested that the increased Ca:P ratios in the rachitic and vitamin D-treated bones may be explained by an increased carbonate deposition.     

Dietary phylloquinone depletion and repletion in postmenopausal women: effects on bone and mineral metabolism

Introduction Vitamin K has been implicated in increased bone fracture risk. Despite a potential role of vitamin K in bone, little is known about the effects of altered dietary phylloquinone intake on the underlying components of bone and mineral metabolism. Methods A 84-day in-house dietary phylloquinone (vitamin K) depletion–repletion study was undertaken in 21 postmenopausal women (mean age: 70 years) to assess the effects of altered vitamin K status on intestinal calcium (Ca) absorption, urinary and serum Ca and phosphorus (P), serum calcemic hormones, and serum biomarkers of bone turnover [osteocalcin and N-telopeptide type 1 collagen cross-links (NTx)] and the response to 1,25-dihydroxyvitamin D treatment (1 μg/day×7 d). Results The group receiving calcitriol treatment (n=11) had higher Ca absorption, urinary Ca, urinary and serum P and serum osteocalcin and lower serum parathyroid hormone (PTH).There were no significant effects of acute (4-week) phylloquinone depletion on response to 1,25-dihydroxyvitamin D treatment or on measures of bone formation or mineral metabolism. However, phylloquinone treatment had a significant effect (p<0.04) on serum NTx. Phylloquinone repletion, up to five times (450 μg phylloquinone per day) the currently recommended adequate intake level of dietary phylloquinone for women, significantly reduced serum NTx (16.8±0.9 nmol bone collagen equivalents (BCE) per liter following repletion vs 18.4±1.1 nmol BCE per liter following depletion; p< 0.01). Conclusions These findings suggest that altering vitamin K status in postmenopausal women by manipulating phylloquinone intake does not have an acute affect on intestinal Ca absorption, renal mineral excretion, or bone formation, but high phylloquinone intake may modestly reduce bone resorption. The impact of high phylloquinone intake on bone mineral density and fracture risk needs to be ascertained in randomized clinical trials.     

The effect of a short course of calcium and vitamin d on bone turnover in older women

Calcium and vitamin D (1200 mg/day + 800 IU) has been shown to reduce hip fracture incidence in older women living in long-term care facilities who had borderline low vitamin D levels. We examined the effect of a short course of calcium and vitamin D on biochemical markers of bone turnover in older community-living women. Twelve community-living women (mean age 75 years) in good general health, without diseases or on medications known to affect bone, were entered into the study. All women were treated with calcium citrate (1500 mg/day of elemental calcium) and vitamin D₃ (1000 IU/day) (Ca + D) for 6 weeks. Biochemical markers of bone turnover were measured in serum and urine collected at baseline (two samples), 5 and 6 weeks on Ca + D, and 5 and 6 weeks after termination of Ca + D. Markers of bone formation were osteocalcin, bone alkaline phosphatase and type I procollagen peptide. Markers of bone resorption were urinary hydroxyproline, free pyridinoline and deoxypyridinoline crosslinks, and N-telopeptides of type I collagen. Parathyroid hormone (PTH) and 25-hydroxyvitamin D were also measured at baseline, 6 weeks on treatment and 6 weeks after termination of treatment. All markers of bone resorption decreased on Ca + D and returned to baseline after termination of Ca + D (p<0.05). Markers of bone formation did not change with Ca + D treatment. PTH decreased on Ca + D and returned to baseline after treatment, and 25-hydroxyvitamin D increased with treatment and remained elevated 6 weeks after the end of treatment. We conclude that Ca + D reduces bone resorption in older women, possibly by suppressing PTH levels.     

An update on vitamin D as related to nephrology practice: 2003

In this article, an up-to-date consideration of vitamin D therapeutics in nephrology is reviewed. The condition of vitamin D insufficiency is defined as the level of serum 25(OH)vitamin D at which vitamin D2 or D3 supplementation leads to a reduction of levels of parathyroid hormone (PTH). The risks of such vitamin D insufficiency in the normal population and likely risks in individuals with chronic kidney disease (CKD) stages 3 and 4 are reviewed. The potential for its safe treatment and prevention using moderate supplements of vitamin D2 or vitamin D3 are outlined. The role of altered "vitamin D nutrition" in leading to the observed greater incidence of secondary hyperparathyroidism in African Americans with ESRD compared to other racial groups is considered. The actions of active vitamin D sterols to augment intestinal absorption of both calcium and phosphorus, the effect to reduce levels of PTH, and to be a factor contributing to the rising incidence of low bone turnover (adynamic bone) are discussed. Growing evidence for contributions of elevated levels of serum calcium, serum phosphorus, and the calcium x phosphorus product as factors contributing to vascular and cardiac calcification in ESRD patients are cited. Questions are raised about whether the current practice of vitamin D usage in ESRD patients might be a contributing factor to such vascular abnormalities. The economic factors that likely affect the usage of intravenous vitamin D sterols in the United States are reviewed. It is recommended that potential adverse vascular effects of vitamin D sterols related to the increments of serum Ca and P be carefully evaluated.     

慢性肾脏病患者血浆成纤维细胞生长因子23水平与骨矿物质代谢的相关性分析

目的观察分析血浆成纤维细胞生长因子23(FGF-23)水平与慢性肾脏病(CKD)患者骨矿物质代谢的相关性。方法选择2015年1月至2017年6月经实验室、影像学等检查确诊为CKD的患者105例作为CKD组,按照肾小球滤过率估计值(eGFR)分为1~5期;选择同期就诊于体检中心且性别、年龄相当的健康体检者30例作为健康组。比较分析两组血红蛋白(Hb)、血浆白蛋白(ALB)、血浆FGF-23、肾小球滤过率(GFR)情况及不同CKD分期患者间血钙、血磷、碱性磷酸酶(ALP)、甲状旁腺激素(PTH)水平,利用Spearman相关分析探讨CKD患者血浆FGF-23水平与血钙、血磷、ALP等指标之间的关系。结果 CKD组的FGF-23显著高于健康组(P<0.05),而Hb、GFR显著低于健康组(P<0.05),并且存在钙磷代谢紊乱、低白蛋白血症。不同CKD分期患者间血磷及血清ALP水平随肾功能的下降有增高趋势,但差异无统计学意义(P>0.05);血钙随GFR下降有下降趋势,但差异无明显统计学意义(P>0.05);PTH水平随CKD分期增高而增高,FGF-23水平随肾功能的降低而增加(P<0.05)。以FGF-23为因变量,以血钙、血磷、ALP、PTH为自变量进行Spearman相关分析。结果显示,FGF-23与血钙(r=-0.77,P<0.05)呈负相关,FGF-23与血磷(r=0.21,P<0.05)、ALP(r=0.85,P<0.01)、PTH(r=0.675,P<0.05)呈正相关。结论 CKD患者外周血FGF-23水平与骨矿物质代谢有一定的相关性。血清FGF-23与血清中钙、磷、PTH具有一定的关系。正常人的血液循环中有FGF-23表达不高,但在高磷饮食、使用活性维生素D过程中,患者血清FGF-23水平也明显升高。FGF-23的调控可能是维生素D、钙、磷、iPTH等多种因素共同作用的结果。通过早期检测血清中FGF-23与钙、磷、ALP的水平,可为患者赢取更多的治疗时间,为患者获益。     

骨质疏松症患者血清骨代谢标志物分析与相关性研究

目的对西安地区部分骨质疏松症患者血清骨代谢标志物进行统计及相关性分析。方法纳入2018年4月至2019年3月经西安市红会医院诊治的原发性骨质疏松症患者295例,检测受试者血清钙(Ca)、磷(P)、碱性磷酸酶(ALP)、维生素D(vitamin D,维生素D)、甲状旁腺素(PTH)、I型前胶原N端肽(P1NP)、β-胶原特殊序列(β-Cross)的水平,运用R统计语言进行统计学处理及Pearson相关性分析。结果在大多数骨质疏松症患者中血清Ca、P是正常的;有20%~30%患者ALP升高;绝大多数患者维生素D缺乏或不足;PTH异常者以升高为主,少数女性患者PTH降低;大多数绝经前女性P1NP、β-Cross正常,在少数绝经前女性及1/3男性中出现升高,小部分绝经后女性出现下降,在小部分绝经后女性中升高。女性骨质疏松症患者中,血清ALP与P1NP、ALP与PTH、维生素D与β-Cross呈正相关(P<0.05),血清Ca与β-Cross、P与ALP、P与β-Cross、P与PTH、ALP与维生素D、ALP与β-Cross、维生素D与P1NP、维生素D与PTH、P1NP与β-Cross呈负相关(P<0.05)。男性骨质疏松症患者中,血清维生素D与β-Cross呈正相关(P<0.05),血清Ca与PTH、ALP与维生素D、维生素D与P1NP、维生素D与PTH、P1NP与β-Cross呈负相关(P<0.05)。结论骨质疏松症患者维生素D缺乏或不足情况严重,了解骨代谢标志物间的相关性有助于更好地理解骨质疏松症骨代谢异常机制。     

Chronic kidney disease mineral and bone disorder in children

Childhood and adolescence are crucial times for the development of a healthy skeletal and cardiovascular system. Disordered mineral and bone metabolism accompany chronic kidney disease (CKD) and present significant obstacles to optimal bone strength, final adult height, and cardiovascular health. Decreased activity of renal 1 alpha hydroxylase results in decreased intestinal calcium absorption, increased serum parathyroid hormone levels, and high-turnover renal osteodystrophy, with subsequent growth failure. Simultaneously, phosphorus retention exacerbates secondary hyperparathyroidism, and elevated levels contribute to cardiovascular disease. Treatment of hyperphosphatemia and secondary hyperparathyroidism improves growth and high-turnover bone disease. However, target ranges for serum calcium, phosphorus, and parathyroid hormone (PTH) levels vary according to stage of CKD. Since over-treatment may result in adynamic bone disease, growth failure, hypercalcemia, and progression of cardiovascular calcifications, therapy must be carefully adjusted to maintain optimal serum biochemical parameters according to stage of CKD. Newer therapeutic agents, including calcium-free phosphate binding agents and new vitamin D analogues, effectively suppress serum PTH levels while limiting intestinal calcium absorption and may provide future therapeutic alternatives for children with CKD.     

Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study

BACKGROUND: Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease. METHODS: This study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of hemodialysis facilities (N= 307) and patients (N= 17,236) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States, Europe, and Japan from 1996 to 2001. RESULTS: Many patients fell out of the recommended guideline range for serum concentrations of phosphorus (8% of patients below lower target range, 52% of patients above upper target range), albumin-corrected calcium (9% below, 50% above), calcium-phosphorus product (44% above), and intact PTH (51% below, 27% above). All-cause mortality was significantly and independently associated with serum concentrations of phosphorus (RR 1.04 per 1 mg/dL, P= 0.0003), calcium (RR 1.10 per 1 mg/dL, P < 0.0001), calcium-phosphorus product (RR 1.02 per 5 mg(2)/dL(2), P= 0.0001), PTH (1.01 per 100 pg/dL, P= 0.04), and dialysate calcium (RR 1.13 per 1 mEq/L, P= 0.01). Cardiovascular mortality was significantly associated with the serum concentrations of phosphorus (RR 1.09, P < 0.0001), calcium (RR 1.14, P < 0.0001), calcium-phosphorus product (RR 1.05, P < 0.0001), and PTH (RR 1.02, P= 0.03). The adjusted rate of parathyroidectomy varied 4-fold across the DOPPS countries, and was significantly associated with baseline concentrations of phosphorus (RR 1.17, P < 0.0001), calcium (RR 1.58, P < 0.0001), calcium-phosphorus product (RR 1.11, P < 0.0001), PTH (RR 1.07, P < 0.0001), and dialysate calcium concentration (RR 0.57, P= 0.03). Overall, 52% of patients received some form of vitamin D therapy, with parenteral forms almost exclusively restricted to the United States. Vitamin D was potentially underused in up to 34% of patients with high PTH, and overused in up to 46% of patients with low PTH. Phosphorus binders (mostly calcium salts during the study period) were used by 81% of patients, with potential overuse in up to 77% patients with low serum phosphorus concentration, and potential underuse in up to 18% of patients with a high serum phosphorus concentration. CONCLUSION: This study expands our understanding of the relationship between altered mineral metabolism and outcomes and identifies several potential opportunities for improved practice in this area.     

Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure.

BACKGROUND: Metabolic bone disease might commence early in the course of renal failure. This study therefore examined the frequency and severity of the skeletal changes in predialysis chronic renal failure by measurements of bone mineral density (BMD), biochemical markers of bone turnover (osteocalcin, bone-specific alkaline phosphatase, carboxy terminal propeptide of type I collagen, and carboxy-terminal telopeptide of type I collagen), parathyroid hormone (PTH), ionized calcium (Ca++), phosphate (P), and vitamin D metabolites. METHODS: The study was performed in 113 patients (male/female: 82/31) with chronic renal diseases [mean glomerular filtration rate (GFR) of 37 ml/min] and in 89 matched, normal control subjects. RESULTS: The patients had significantly (P<0.05) reduced BMD in the spine (-6.3%), the femur (-12.1%), the forearm (-5.7%), and the total body (-4.2%) as compared with the control subjects. Dividing the patients into quartiles according to GFR revealed that BMD decreased with the gradual decline in renal function at all the measured skeletal sites, but was most pronounced in the femur: 0.63+/-0.03, 0.74+/-0.02, 0.77+/-0.02, and 0.82+/-0.03 g/cm2 in each quartile from lowest to highest GFR compared with 0.82+/-0.02 g/cm2 in the control group (P<0.0001). All of the measured bone markers showed increasing plasma levels with the more advanced stages of renal failure. Serum PTH and serum P levels increased, whereas serum Ca++ and 1,25-dihydroxyvitamin D decreased. BMD Z-scores of the femur and of the forearm correlated to the biochemical markers and to PTH (P<0.05 to P<0.0001). The biochemical markers all showed strong correlations to PTH, also when corrected for the effect of the decline in GFR (r = 0.40 to 0.92, P<0.01 to P< 0.0001). CONCLUSION: Skeletal changes are initiated at an early stage of chronic renal failure, as estimated from reduced BMD and elevated levels of PTH and from the biochemical markers of both bone formation and bone resorption.