Paricalcitol capsules for the control of secondary hyperparathyroidism in chronic kidney disease

Secondary hyperparathyroidism is a common complication of patients with chronic kidney disease. Treatment with calcitriol, the active form of vitamin D, reduces parathyroid hormone levels, but may result in elevations in serum calcium and phosphorus. New vitamin D analogues have been developed to reduce parathyroid hormone secretion without concomitant hypercalcaemia and hyperphosphataemia. Recent data from studies with paricalcitol capsules, the oral formulation of 19-nor-1,25(OH)₂D₂, show a significant reduction in parathyroid hormone levels with no change in calcium and phosphorus levels when compared with placebo. Paricalcitol also compares favourably to other oral vitamin D analogues, effectively decreasing parathyroid secretion with less hypercalcaemia and hypercalciuria than other agents.     

Cinacalcet HCl: a novel therapeutic for hyperparathyroidism

Hyperparathyroidism (HPT) is a significant clinical concern for patients with a variety of diseases, notably the secondary HPT associated with chronic kidney disease requiring dialysis. Secondary HPT is associated with elevated para-thyroid hormone (PTH) levels, decreased levels of 1,25 dihydroxyvitamin D, and disordered mineral levels (usually high calcium and phosphorus). If not controlled, secondary HPT can result in bone disease, vascular calcification, and ultimately, patient mortality. Established, conventional therapies, such as 1,25dihydroxyvitamin D analogues (vitamin D analogues) and phosphate binders, have proven to be inadequate in enabling patients to meet the National Kidney Foundation's-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) treatment goals for PTH, calcium and phosphorus levels. A novel therapeutic, cinacalcet HCl (formerly AMG 073; Sensipar in the US and Mimpara in Europe; Amgen, Inc.), binds directly to the calcium-sensing receptor (CaR) on the cells of the parathyroid gland, increasing the receptor's sensitivity to calcium and reducing PTH, serum calcium and phosphorus levels. Treatment with cinacalcet in clinical trials has safely and effectively improved achievement of the NKF-K/DOQI goals. Cinacalcet has also reduced serum calcium levels in patients with primary HPT, including parathyroid carcinoma, in the clinical trial setting. Evidence suggesting the utility of cinacalcet in these diseases and the potential for additional therapeutic applications will be discussed.     

Pathogenesis and treatment of secondary hyperparathyroidism in dialysis patients: the role of paricalcitol

Hemodialysis (HD) patients are commonly affected by secondary hyperparathyroidism (SHPT), in which 3 well-known factors are usually involved: hypocalcemia, hyperphosphatemia and calcitriol deficiency. Classically, high parathyroid hormone (PTH) levels cause bone-associated diseases, such as osteitis fibrosa and renal osteodystrophy, but more recently it has been demonstrated the link between SHPT and a systemic toxicity, with a major role in determining cardio-vascular disease, including arterial calcification, endocrine disturbances, compromised immune system, neurobehavioral changes, and altered erythropoiesis. Treatment with calcitriol (CT), the active form of vitamin D, reduces parathyroid hormone (PTH) levels, but may result in elevations in serum calcium (Ca) and phosphorus (P), increasing the risk of cardio-vascular calcification in the HD population. Several new vitamin D analogs have been developed and investigated with the rationale to treat SHPT with a reduced risk of hypercalcemia and hyperphosphatemia in HD patients. Paricalcitol (1,25-dihydroxy-19-nor-vitamin D(2), 19-Nor-D(2)) is a vitamin D analog that suppresses PTH secretion with minimal increases on serum calcium and phosphate levels. It was demonstrated that paricalcitol prevents vascular calcification in experimental models of renal failure, compared with calcitriol. Furthermore, 19-Nor-D(2) is the first analog approved for use in HD patients and is available for i.v. and oral administration, commonly 3 times weekly after HD. The purpose of the present review is to analyze the pathogenesis and treatment of SHPT in HD patients, and the role of paricalcitol in the prevention of arterial calcification.     

Management of hyperphosphataemia in dialysis patients: role of phosphate binders in the elderly

Phosphorus control remains a relevant clinical problem in dialysis patients. With age, however, serum phosphorus level decreases significantly because of a spontaneous decrease in protein intake. Older patients usually need lower doses of phosphorus binders. Nevertheless, hyperphosphataemia is observed in a quarter of patients aged >65 years. Phosphorus retention is related to an imbalance between phosphorus intake and removal by dialysis, and is usually aggravated when vitamin D analogues are employed. Hyperphosphataemia induces secondary hyperparathyroidism and the development of osteitis fibrosa. Recent publications describe an association between phosphorus retention and increased calcium and phosphorus product (Ca2+ x P), with significant progression of tissue calcification and higher mortality risk. Dietary intervention, phosphorus removal during dialysis and phosphorus binders are current methods for the management of hyperphosphataemia. However, the phosphorus removed by standard haemodialysis is insufficient to achieve a neutral phosphorus balance when protein intake is >50 g/day. Additional protein restriction may impose the risk of a negative protein balance. More frequent dialysis may help to control resistant hyperphosphataemia. Phosphorus binders constitute the mainstay of serum phosphorus level control in end-stage renal disease patients. Aluminium-based phosphorus binders, associated with toxic effects, have largely been substituted by calcium-based phosphorus binders. However, widespread use of calcium-based phosphorus binders has evidenced the frequent appearance of hypercalcaemia and long-term progressive cardiovascular calcification. Sevelamer, a relatively new phosphorus binder, has proved efficacious in lowering serum phosphorus and parathyroid hormone (PTH) levels without inducing hypercalcaemia. Furthermore, several investigators have reported that sevelamer may prevent progression of coronary calcification. However, its efficacy in severe cases of hyperphosphataemia remains to be confirmed in large series. There are no specific guidelines for phosphorus control in the elderly. Until more information is available, levels of mineral metabolites should be targeted in the same range as those recommended for the general population on dialysis (calcium 8.7-10.2 mg/dL, phosphorus 3.5-5.5 mg/dL and Ca2+ x P 50-55 mg2/dL2). PTH values over 120 ng/L help to avoid adynamic bone disease. Since elderly patients have a higher incidence of adynamic bone (which buffers less calcium) and vascular calcification, sevelamer should be the phosphorus binder of choice in this population; but sevelamer is costly and its long-term efficacy has not been definitively validated. Patients with low normal levels of calcium may receive calcium-based phosphorus binders with little risk. Patients with low values of PTH and high normal calcium should receive sevelamer. Tailored combinations of calcium-based phosphorus binders and sevelamer should be considered, and calcium dialysate concentration adjusted accordingly.     

Vitamin D receptor activator selectivity in the treatment of secondary hyperparathyroidism: understanding the differences among therapies

Secondary hyperparathyroidism (SHPT) is a common and serious consequence of chronic kidney disease (CKD). SHPT is a complex condition characterised by a decline in 1,25-dihydroxyvitamin D and consequent vitamin D receptor (VDR) activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drugs used for treatment of SHPT: (i) nonselective VDR activators or agonists (VDRAs); (ii) selective VDRAs; and (iii) calcimimetics. The VDRAs act on the VDR, whereas the calcimimetics act on the calcium-sensing receptor. Calcimimetics are commonly used in conjunction with VDRA therapy. By virtue of the differences in their chemical structure, the nonselective and selective VDRAs differ in their effects on gene expression, and ultimately parathyroid gland, bone and intestine function. Medications in all three classes are effective in suppression of PTH; however, clinical studies show that calcimimetics are associated with an unfavourable tolerability profile and hypocalcaemia, whereas nonselective VDRAs, and to a lesser extent selective VDRAs, are associated with dose-limiting hypercalcaemia and hyperphosphataemia. Selective VDRAs also have minimal undesirable effects on calcium absorption in the intestine, and calcium and phosphorus mobilisation in the bone compared with nonselective VDRAs. Calcium load in patients with CKD can lead to vascular calcification, accelerated progression of cardiovascular disease and increased mortality. High serum phosphorus levels are also associated with adverse effects on cardiorenal function and survival. Recent evidence suggests that VDRAs are associated with a survival benefit in CKD patients, with a more favourable effect with selective VDRAs than nonselective VDRAs. Paricalcitol, a selective VDRA, is reported to exert specific effects on gene expression in various cell types that are involved in vascular calcification and the development of coronary artery disease. This article examines the molecular mechanisms that determine selectivity of VDRAs, and reviews the evidence for clinical efficacy, safety and survival associated with the three drug classes used for treatment of SHPT in CKD patients.     

Paricalcitol: a review of its use in the management of secondary hyperparathyroidism

Paricalcitol (Zemplar) is a synthetic vitamin D(2) analogue that inhibits the secretion of parathyroid hormone (PTH) through binding to the vitamin D receptor. It is approved in the US and in most European nations for intravenous use in the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure in adult, and in the US paediatric, patients.Paricalcitol effectively reduced elevated serum PTH levels and was generally well tolerated in children and adults with secondary hyperparathyroidism associated with chronic renal failure. In well designed clinical trials, paricalcitol was as effective as calcitriol and as well tolerated in terms of the incidence of prolonged hypercalcaemia and/or elevated calcium-phosphorus product (Ca x P). Thus, paricalcitol is a useful option for the management of secondary hyperparathyroidism in adults and children with chronic renal failure.     

Calcitriol dosage in osteomalacia, hypoparathyroidism and attempted treatment of myositis ossificans progressiva

Mineral retention was measured during 39 metabolic balance studies in 34 patients with nutritional osteomalacia or late rickets; they were divided into 5 treatment groups consisting of oral vitamin D, artificial ultra-violet irradiation, 25-hydroxycholecalciferol (calcifediol), 1 alpha-hydroxycholecalciferol (alfacalcidol) and 1 alpha, 25-hydroxycholecalciferol (calcitriol). With the 1 alpha-hydroxylated derivatives, initial dosage of 2 to 6 micrograms daily was required to achieve optimal healing rates by comparison with other responses. Mineral retention was markedly enhanced by supplementation with microcrystalline hydroxyapatite compound (MCHC); untreated X-linked hypophosphataemic rickets healed in 7 weeks on 10 micrograms alfacalcidol daily and 6 grams MCHC daily without developing hypercalcaemia. By contrast, adult-presenting hypophosphataemic osteomalacia developed early hypercalcaemia on the same treatment; additional phosphate supplementation, without changing other treatment, abolished hypercalcaemia and improved calcium retention. A long-term crossover trial of the vitamins D in 6 patients with hypoparathyroidism suggested that relative potencies were as follows (assigning to vitamin D an arbitrary potency of l): vitamin D2 (or D3) l: dihydrotachysterol (DHT) 3: calcifediol 10: alfacalcidol 750: calcitriol 1500. The two-fold superiority of calcitriol over alfacalcidol was evident. Calcifediol and vitamin D controlled plasma calcium at comparable levels of circulating 25-hydroxyvitamin D (25-OH-D), elevated 25-OH-D persisting at least 1 to 2 years after discontinuing long-term (greater than 4 years) vitamin D. In 2 patients with myositis ossificans progressiva treated with 10 to 20 micrograms calcitriol daily, hypercalcaemia was minimized by a low-calcium diet supplemented with cellulose phosphate, suggesting that bone resorption did not play a major role in vitamin D intoxication. Net mineral loss was documented in a young male patient but not in a menopausal female, suggesting that calcitriol treatment was not likely to produce post-menopausal osteoporosis.     

Medical treatment of primary, secondary, and tertiary hyperparathyroidism

Hyperparathyroidism is a condition with elevated parathyroid hormone (PTH). The increase may be due to a) primary hyperparathyroidism which is caused by adenoma of one or more parathyroid glands or hyperplasia of all four glands, b) secondary hyperparathyroidism, which may be caused by deficiency in vitamin D or uremia, and 3) tertiary hyperparathyroidism, which most often is the result of a long-standing, severe secondary hyperparathyroidism, which has turned autonomous once the cause of the secondary hyperparathyroidism has been removed. Many new treatment options have been introduced in recent years. Cinacalcet is calcium sensing receptor agonist, which by stimulating the receptor decreases PTH and calcium levels. It may be used in primary hyperparathyroidism, secondary hyperparathyroidism caused by uremia, which may not be controlled with calcium and activated vitamin D. It may also be used in tertiary hyperparathyroidism. Newer analogues of vitamin D such as paricalcitol have also been introduced, which may have an advantage over traditional compounds such as alphacalcidol and calcitriol.     

Pharmacological and clinical trial data on a novel phosphate-binding polymer (sevelamer hydrochloride), a medicine for hyperphosphatemia in hemodialysis patients

Hyperphosphatemia is one of the major complications of hemodialysis patients and plays a key role in the pathogenesis of cardiovascular calcification and secondary hyperparathyroidism. Dietary phosphate restriction and removal of phosphate by dialysis are insufficient to control hyperphosphatemia. Therefore, almost all patients undergoing hemodialysis should take oral phosphate binders. Sevelamer hydrochloride (sevelamer) is a novel phosphate-binding polymer that contains neither aluminum nor calcium, and it is not absorbed from the gastrointestinal tract. In rat models with progressive chronic renal insufficiency, in addition to lowering effects on serum levels of phosphorus, calcium x phosphorus product, and parathyroid hormone, dietary treatment of sevelamer can prevent parathyroid hyperplasia, vascular calcification, high turnover bone lesion, and renal functional deterioration. In clinical studies with hemodialysis patients, sevelamer lowers serum phosphorus and calcium x phosphorus product without any incidence of hypercalcemia. Switching calcium-containing phosphate binders to sevelamer can decrease the percentage of hypoparathyroidism and hyperparathyroidism by negative calcium balance and increased dosage of vitamin D, respectively. Sevelamer also decreases serum low-density lipoprotein cholesterol levels by its bile acid-binding capacity. A long-term clinical study has demonstrated that the progression of coronary and aortic calcification in hemodialysis patients is attenuated by sevelamer. Thus, sevelamer offers the promise of impacting cardiac calcification and thereby reducing morbidity and mortality of hemodialysis patients.     

Calcium agonists in hyperparathyroidism

Primary hyperparathyroidism (PHPT), in addition to cancer, represents an important cause of hypercalcaemia in the general population. Furthermore, hypercalcaemia, in the course of uraemic HPT, represents the late stage of chronic renal failure refractory to therapy. Neck surgery is still the only curative approach for these forms of HPT and medical treatment rarely exhibits an effective control on HPT and HPT-dependent hypercalcaemia. Moreover, some HPT patients may not undergo neck surgery due to the presence of other concomitant disorders. Therefore, more effective therapeutic approaches are needed than the commonly used 'palliative' treatments. The identification of a specific membrane receptor able to bind extracellular calcium on cells of the parathyroid and other tissues has allowed the development of new molecules acting through this receptor to reduce both parathyroid hormone secretion and the rate of parathyroid cell proliferation. Consequently, they may substantially contribute to the regulation of bloodstream calcium levels in HPT patients. Preliminary results obtained in clinical trials are encouraging, demonstrating a good efficacy and safety of such drugs. However, more in vitro and in vivo, as well as long-term clinical studies, will be necessary before they can be commonly used as therapeutical molecules in the clinical practice.     

Calcium agonists in hyperparathyroidism

Primary hyperparathyroidism (PHPT), in addition to cancer, represents an important cause of hypercalcaemia in the general population. Furthermore, hypercalcaemia, in the course of uraemic HPT, represents the late stage of chronic renal failure refractory to therapy. Neck surgery is still the only curative approach for these forms of HPT and medical treatment rarely exhibits an effective control on HPT and HPT-dependent hypercalcaemia. Moreover, some HPT patients may not undergo neck surgery due to the presence of other concomitant disorders. Therefore, more effective therapeutic approaches are needed than the commonly used ‘palliative’ treatments. The identification of a specific membrane receptor able to bind extracellular calcium on cells of the parathyroid and other tissues has allowed the development of new molecules acting through this receptor to reduce both parathyroid hormone secretion and the rate of parathyroid cell proliferation. Consequently, they may substantially contribute to the regulation of bloodstream calcium levels in HPT patients. Preliminary results obtained in clinical trials are encouraging, demonstrating a good efficacy and safety of such drugs. However, more in vitro and in vivo, as well as long-term clinical studies, will be necessary before they can be commonly used as therapeutical molecules in the clinical practice.     

Cinacalcet HCl: a calcimimetic agent for the management of primary and secondary hyperparathyroidism

Cinacalcet HCl (AMG 073) is an investigational oral calcimimetic drug currently being evaluated for the treatment of primary and secondary hyperparathyroidism (HPT). Calcimimetics bind to the calcium-sensing receptors of the parathyroid glands and lower the sensitivity for receptor activation by extracellular calcium, thereby diminishing parathyroid hormone release. Cinacalcet HCl has demonstrated efficacy in controlling the hypercalcaemia of severe primary HPT and in reducing parathyroid hormone levels in patients with secondary HPT. Asymptomatic dose-dependent hypocalcaemia has occurred in some clinical trials. This drug has a favourable pharmacokinetic profile compared to its precursors and will prove useful as an additional/alternative agent in patients with primary and secondary HPT.     

Secondary hyperparathyroidism in children with chronic renal failure: pathogenesis and treatment

Despite advances in the management of patients with chronic renal failure, histologic features associated with secondary hyperparathyroidism remain the predominant skeletal findings; however, over the last decade the prevalence of adynamic bone has increased in both adult and pediatric patients with chronic renal failure. The management of children with secondary hyperparathyroidism and mild to moderate chronic renal failure should be started early, and should include correction of hypocalcemia and metabolic acidosis, maintenance of age-appropriate serum phosphorus levels, and institution of vitamin D therapy when serum intact parathyroid hormone (PTH) measurements are elevated to maintain the blood levels within normal limits; however, in children undergoing chronic dialysis therapy, the current recommendation is to maintain the serum intact PTH levels at least 2-4 times the upper limits of normal to prevent the development of low bone turnover disease. Serum calcium, phosphorus, alkaline phosphatase, and PTH levels should be monitored frequently, especially in infants and very young children. Discontinuation or reduction of vitamin D should be considered when there is a rapid decline in PTH levels, persistent elevation in serum calcium and serum phosphorus levels, and a significant diminution in alkaline phosphatase levels. In addition, a reduction in the calcium concentration of the dialysis fluid, and judicious use of calcium-containing salts as phosphate binding agents should also be performed in these patients. Although not yet extensively used in pediatric patients with secondary hyperparathyroidism, several therapeutic alternatives, such as the less calcemic vitamin D analogs, including paricalcitol [19-nor-1,25-(OH)(2)D(2)] and doxercalciferol [1-alpha-(OH)(2)D(2)], calcimimetics, and the availability of a calcium-free, aluminum-free phosphate binder such as sevelamer hydrochloride and lanthanum carbonate, may play significant roles in the future management of children with secondary hyperparathyroidism to promote linear growth, prevent parathyroid gland hyperplasia, avoid calciphylaxis and, in the long run, avert vascular calcifications.     

Cinacalcet hydrochloride

Oral cinacalcet hydrochloride (HCl) [Sensipar, Mimpara] is the first in a new class of therapeutic agents, the calcimimetics, and has a novel mechanism of action. It directly modulates the principal regulator of parathyroid hormone (PTH) secretion, namely the calcium-sensing receptor (CaR) on the chief cells in the parathyroid gland. Cinacalcet HCl reduces circulating PTH levels by increasing the sensitivity of the CaR to extracellular calcium. In three pivotal phase III, 26-week, randomised, double-blind, multicentre trials in chronic kidney disease (CKD) patients (n = 1136) on dialysis with uncontrolled secondary hyperparathyroidism (HPT), a significantly higher proportion of oral cinacalcet HCl 30-180 mg/day than placebo recipients achieved a reduction in intact PTH levels to < or =250 pg/mL. Cinacalcet HCl treatment also simultaneously lowered serum calcium and phosphorus, and calcium-phosphorous product levels. Notably, cinacalcet HCl proved effective in a broad range of CKD patients on dialysis with uncontrolled secondary HPT, regardless of disease severity, duration of dialysis treatment, dialysis modality, race, age, gender, or concurrent phosphate binder or vitamin D sterol use. Cinacalcet HCl (60-360 mg/day) also reduced elevated serum calcium levels by > or =1 mg/dL in 15 of 21 (71%) patients with parathyroid carcinoma in an open-label, multicentre, dose-titration trial. Cinacalcet HCl was generally well tolerated in clinical trials. Most treatment-emergent adverse events were mild to moderate in severity.     

Cinacalcet HCl: a calcimimetic agent for the management of primary and secondary hyperparathyroidism

Cinacalcet HCl (AMG 073) is an investigational oral calcimimetic drug currently being evaluated for the treatment of primary and secondary hyperparathyroidism (HPT). Calcimimetics bind to the calcium-sensing receptors of the parathyroid glands and lower the sensitivity for receptor activation by extracellular calcium, thereby diminishing parathyroid hormone release. Cinacalcet HCl has demonstrated efficacy in controlling the hypercalcaemia of severe primary HPT and in reducing parathyroid hormone levels in patients with secondary HPT. Asymptomatic dose-dependent hypocalcaemia has occurred in some clinical trials. This drug has a favourable pharmacokinetic profile compared to its precursors and will prove useful as an additional/alternative agent in patients with primary and secondary HPT.     

Calcitriol dosage in osteomalacia,hypoparathyroidism and attempted treatment of myositis ossificans progressiva

Summary

Mineral retention was measured during 39 metabolic balance studies in 34 patients with nutritional osteomalacia or late rickets; they were divided into 5 treatment groups consisting of oral vitamin D, artificial ultra-violet irradiation, 25-hydroxychole-calciferol {calcifediol), 1 α-hydroxycholecalciferol (alfacalcidol) and 1α,25-dihydroxy-cholecalciferol (calcitriol). With the 1 α-hydroxylated derivatives, initial dosage of 2 to 6 μg daily was required to achieve optimal healing rates by comparison with other responses. Mineral retention was markedly enhanced by supplementation with micro-crystalline hydroxyapatite compound (MCHC); untreated X-linked hypophosphataemic rickets healed in 7 weeks on 10 μg alfacalcidol daily and 6?g MCHC daily without developing hypercalcaemia. By contrast, adult-presenting hypophosphataemic osteomalacia developed early hypercalcaemia on the same treatment; additional phosphate supplementation, without changing other treatment, abolished hypercalcaemia and improved calcium retention. A long-term crossover trial of the vitamins D in 6 patients with hypoparathyroidism suggested that relative potencies were as follows {assigning to vitamin D an arbitrary potency of 1): vitamin D₂ (or D₃) 1: dihydrotachysterol (DHT) 3: calcifediol 10: alfacalcidol 750: calcitriol 1500. The two-fold superiority of calcitriol over alfacalcidol was evident. Calcifediol and vitamin D controlled plasma calcium at comparable levels of circulating 25-hydroxyvitamin D (25-OH-D), elevated 25-OH-D persisting at least 1 to 2 years after discontinuing long-term (>4 years) vitamin D. In 2 patients with myositis ossificans progessiva treated with 10 to 20 μg calcitriol daily, hypercalcaemia was minimized by a low-calcium diet supplemented with cellulose phosphate, suggesting that bone resorption did not play a major role in vitamin D intoxication. Net mineral loss was documented in a young male patient but not in a menopausal female, suggesting that calcitriol treatment was not likely to produce post-menopausal osteoporosis.     

Toxicity of Vitamin D Analogues in Rats Fed Diets with Standard or Low Calcium Contents

Abstract: Sprague-Dawley rats were fed either a standard diet with 0.9/0.7% Ca/P or a semisynthetic low-calcium diet with 0.5/0.4% Ca/P and treated orally for 28 days with 1α-hydroxycholecalciferon [lα(OH)D₃], a synthetic analogue of the physiologically active form of vitamin D₃, lα,25-dihydroxycholecalciferol [1α,25(OH)₂D₃], at dose levels of 0.2 and 2.0 μg/kg/day. The high dose caused severe hypercalcaemia with retarded growth, nephrosis, and structural bone changes in rats fed the standard diet. The same dose caused only slight hypercalcaemia without growth retardation or bone changes, and only minimally affected the kidneys in rats fed the low-calcium diet. Hypercalcaemia with less pronounced pathological changes was found in the standard diet low-dose rats, whereas no hypercalcemia or pathological changes were found in the low-calcium diet low-dose group. The rats fed the low-calcium diet tolerated 1α(OH)D₃ at dose levels up to 10 times higher than rats on the standard diet. The use of diets low in calcium and low in phosphorus will thus allow the administration of higher dosages of vitamin D compounds without causing hypercalcaemia. This may permit a better evaluation of the pharmacologic and toxic effects not directly associated with the calcium-regulating properties of vitamin D metabolites and analogues.     

慢性肾病合并矿物质与骨代谢紊乱的发病机制、临床诊断与治疗

慢性肾病（CKD）患者的血液钙、磷、甲状旁腺激素、维生素D、成纤维细胞生长因子-23、等生化因子的水平会发生异常,这不仅能导致长期的系统性并发症,还会引起骨矿物质代谢失衡,造成骨损伤,增加慢性肾病合并矿物质与骨代谢紊乱（CKD-MBD）的患病率和死亡率。本文对CKD-MBD的发病机制、临床诊断与治疗策略作一综述。     

特发性甲状旁腺功能减退症临床分析

目的 总结特发性甲状旁腺功能减退症(IHP)的临床特征.方法 回顾性分析1978年9月至2006年9月于北京协和医院内分泌科门诊就诊的53例IHP患者的临床表现及生化指标.结果 53例IHP患者血钙(1.54±0.23) mmol/L,血浆游离钙(0.70±0.14) mmol/L,血磷(2.1±0.4) mmol/L,甲状旁腺激素2.4(1～15.6) ng/L;各临床表现发生情况如下:手足搐搦为90.1％ (48/53),癫(癎)发作为41.5％ (22/53),智力减退为22.9％(11/48);白内障50.0％(12/24);颅内钙化42.5％(17/40).口服钙剂和维生素D制剂纠正低钙血症可以消除低血钙所造成的神经精神症状.结论 IHP是因甲状旁腺激素产生减少而引起的钙、磷代谢异常,长期口服钙剂和维生素D制剂可控制病情.