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In chronic renal failure several factors affect bone homeostasis leading to the development of renal osteodystrophy. Common calcitropic hormone derangements in renal failure play a central role in bone structure and mineral defects, which in turn accompany osteodystrophy frequently resulting in low bone mineral density (BMD) values. However, patients with end-stage renal disease (ESRD) suffer from several comorbidities, which may partly account for renal bone disease lesions. Hypogonadism in particular accompanies chronic renal failure frequently and exerts an additive effect on bone loss potential. Sex hormones contribute to the equilibrium of osteotropic hormones and cytokines, exerting a protective action on bone tissue. Estrogens have a regulatory effect on bone metabolism in women with renal failure as well. Hypogonadal ESRD women experience a higher bone turnover and more significant bone mass decrements than ESRD women with relatively normal hormone profile and menstrual habits. Female hemodialysis patients have lower BMD values than male patients on average, probably because of menstrual cycle irregularities. However, hypogonadal ESRD men may also experience bone mineral deficits and the severity of hypogonadism may correlate to their bone mineral status. Hormone replacement therapy (HRT) appears to reverse bone mineral loss to some extent in both sexes. In conclusion hypogonadism in renal failure contributes to the bone structure and mineral defects as well as the low-energy fracture risk, reflected in BMD measurements. HRT in ESRD patients should therefore not be overlooked in these patients in the face of their significant comorbidities.

Phosphorus is one of the important factors that accelerate the progression of chronic kidney disease. Phosphorus restriction or phosphate binders have been reported to have the ability to prevent the progression of chronic kidney disease. FGF23 is a circulating factor that regulates renal phosphorus reabsorption and 1 alpha-hydroxylase activity. We focused on the phosphaturic activity of FGF23 and investigated whether a pharmacological dose of FGF23 is beneficial to the progression of renal insufficiency in uremic rats. To this end, we administered one of the mutant FGF23 expression plasmids into irreversible Thy1 rats. Chronic renal failure rats were established by intravenous injection of anti-rat CD90 (Thy1.1) monoclonal antibody to unilaterally nephrectomized Wistar rats. The rats were then intravenously injected every 2 wk with a naked DNA solution containing 10 microg of MOCK vector or a mutant FGF23 expression plasmid for 13 wk. Renal function was assessed biochemically and histopathologically. Mutant FGF23 significantly decreased serum creatinine and serum urea nitrogen. The marked glomerular sclerosis observed in uremic rats receiving the MOCK vector was ameliorated in rats treated with mutant FGF23. However, mutant FGF23 not only significantly decreased serum 1,25(OH)(2)D and calcium but also aggravated high-turnover renal osteodystrophy from extremely high levels of PTH. These results might be a result of the mechanisms of FGF23 such as phosphaturic activity and lowering the level of 1,25(OH)(2)D. In conclusion, mutant FGF23 prevented the progression of chronic renal failure by regulating serum phosphorus but aggravated renal osteodystrophy from the lowered levels of 1,25(OH)(2)D.

Pseudohypoparathyroidism (PHP) is characterized by hypocalcemia and hyperphosphatemia due to resistance to parathyroid hormone (PTH). Patients with PHP-Ia often show additional hormone resistance and characteristic physical features that are collectively termed Albright's hereditary osteodystrophy (AHO). These features are also present in pseudopseudohypoparathyroidism (PPHP), but patients with this disorder do not show hormone resistance. PHP-Ib patients, on the other hand, predominantly show renal PTH resistance and lack features of AHO. From the genetic point of view, PHP-I is caused by defects in the GNAS gene or in the 5' region of this gene locus. PHP-Ia is caused by heterozygous inactivating mutations in any of the 13 exons codifying the alpha subunit of the stimulatory guanine nucleotide-binding protein (Gsα), while PHP-Ib is due to alterations in the methylation pattern of the 5' regions of the locus, usually associated with upstream microdeletions that are maternally transmitted. The imprinting pattern that affects the GNAS locus has important implications for the inheritance pattern and consequently for appropriate genetic counselling.

Background/Aims: Few clinical trials conducted with cinacalcet have thoroughly addressed its effects of on bone metabolism. We assessed the effects of cinacalcet on bone markers in Japanese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). Methods: 200 Japanese HD patients with intact PTH (iPTH) levels ≥300 pg/ml were enrolled. The dose of cinacalcet was titrated from 25 up to 100 mg/day to achieve iPTH levels ≤250 pg/ml for 52 weeks. Results: At the end of the study visit, 57.8% of patients (115/199) had achieved iPTH levels ≤250 pg/ml. Serum Ca, phosphorus (P) and Ca × P levels decreased rapidly and were maintained throughout the study. At week 52, all bone metabolic markers levels had decreased significantly from baseline. Although bone resorption markers gradually decreased throughout the study period, bone alkaline phosphatase significantly increased during the first 4 weeks and then gradually decreased. Conclusions: The time courses of changes in bone markers after cinacalcet treatment resembled those observed after surgical parathyroidectomy (PTx), sometimes described as the hungry bone syndrome, indicating that cinacalcet treatment induces a rapid recovery in bone response to calcium. In addition, long-term efficacy and safety of cinacalcet were also observed in Japanese patients undertaking long-term hemodialysis (167.0 ± 81.4 months).

Renal osteodystrophy (ROD) develops early in the course of chronic kidney disease (CKD). With improving patient survival it's importance and relevance has increased. The last published bone biopsy data in children prior to renal replacement therapy (RRT) was in 1982, which demonstrated abnormal histology in all patients with a glomerular filtration rate (GFR)20 ml/min per 1.73 m(2). Studies investigating the relationship between bone histology and parathyroid hormone levels (PTH) and/or growth in children with CKD are few (seven). These were mostly undertaken in patients already initiated on RRT-dialysis. We investigated the presence of ROD in children at the commencement of RRT and to investigate any relationship between histology, growth and PTH levels. Following double tetracycline labelling, bone biopsies were taken from patients at the time of RRT surgery. Histological classification was based on the newly proposed turnover/mineralisation/volume (TMV) system. Eleven patients underwent bone biopsy. Patients were followed for an average of 1.1 years (0.5-1.8) prior to biopsy over an average of eight clinic visits (3-14), when routine biochemical data were collected. Time-integrated median calcium, phosphate and PTH levels were calculated. PTH levels were within the normal range in two patients with low turnover, 1.1-1.4 times the upper limit of normal (ULN) in three with mixed osteodystrophy and2.9 times the ULN in four patients with high bone turnover. There was no relationship between bone turnover and growth. The presence of ROD was universal in these children with severe CKD. Low bone turnover was associated with normal-range mean PTH levels, and high bone turnover occurred at lower PTH levels than current guidelines would suggest.

More than 50% of cancer patients survive for more than 5 years, owing to modern and effective treatment. Therefore, long-term sequelae of treatment are more frequently seen than in the past. Such effects on normal tissue may both mimic and obscure tumor recurrences. Besides the direct consequences of surgery, tissue damage due to radiation or chemotherapy frequently cause problems in differential diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy changes in bone marrow signals in MRI. The most devastating long-term complications are secondary cancers and leukemia induced by both radiotherapy and chemotherapy.

Chronic renal disease is characterised by progressive and irreversible loss of renal function. A number of systemic and oral complications are associated with chronic renal disease. We report a rare case of jaw enlargement caused by the simultaneous presence of osteitis fibrosis and brown tumour secondary to hyperparathyroidism. Both conditions are related to increased levels of parathyroid hormone and dental surgeons should be aware of this important complication associated with chronic renal disease.

Otospongiosis is an osteodystrophy of the temporal bone, characterized by disordered neoformation and deposition of bone, characterized by the presence of a progressive conductive, sensorineural or mixed hearing loss and tinnitus. Typically, otospongiosis presents as a slowly progressive conductive hearing loss in the third to fourth decade of life. Uncommonly children and adolescents may also have conductive or sensorineural hearing loss caused by otosclerosis. We describe a case of an 11-year-old patient, with progressive unilateral conductive hearing loss for 5 years. The otoscopic examination revealed a positive Schwartz's sign in the left ear. Audiometry, impedanciometry and CT scan showed characteristics that suggested otospongiosis. We reviewed clinical aspects, diagnosis and the therapeutic approach for otospongiosis in children.

SummaryOtospongiosis is an osteodystrophy of the temporal bone, characterized by disordered neoformation and deposition of bone, characterized by the presence of a progressive conductive, sensorineural or mixed hearing loss and tinnitus. Typically, otospongiosis presents as a slowly progressive conductive hearing loss in the third to fourth decade of life. Uncommonly children and adolescents may also have conductive or sensorineural hearing loss caused by otosclerosis. We describe a case of an 11-year-old patient, with progressive unilateral conductive hearing loss for 5 years. The otoscopic examination revealed a positive Schwartz's sign in the left ear. Audiometry, impedanciometry and CT scan showed characteristics that suggested otospongiosis. We reviewed clinical aspects, diagnosis and the therapeutic approach for otospongiosis in children.

Bone disease after kidney transplantation has a complex pathophysiology and heterogeneous histology. Pre-existing renal osteodystrophy may not resolve completely, but continue or evolve into a different osteodystrophy. Rapid bone loss immediately after transplant can persist, at a lower rate, for years to come. These greatly increase the risk of bone fracture and vertebral collapse. Hypovitaminosis D, hyperparathyroidism and hyperaluminemia may resolve after kidney transplant, but many patients have other risk factors of bone loss, such as steroids usage, hypogonadism, persistent hyperparathyroidism, poor allograft function, aging, and chronic diseases. Clinical management requires a comprehensive approach to address the underlying and ongoing disease processes. Successful prevention of bone loss has been shown with vitamin D analogues, bisphosphonates and calcitonin. Novel approaches to restore the normal bone remodeling and improve the bone quality may be needed in order to effectively decrease bone fractures in kidney transplant recipients.

By the time patients require dialysis replacement therapy, nearly all chronic kidney diseases (CKD) patients are affected with uremic bone diseases. High-turnover osteodystrophy can be prevented; patients with CKD should be monitored for imbalances in calcidiol (25 OH vitamin D), calcium, and phosphate homeostasis. We aimed to determine the effect of a monthly oral 300,000 IU vitamin D(3) (cholecalciferol) supplementation on the uremic bone diseases (UBD) markers such as iPTH and alkaline phosphatase in CKD patients. Among a total of 70 patients under treatment in the nephrology unit, 40 predialysis CKD patients (mean age of 49 +/- 14, male/female 20/20) were included the study. The patients were randomly divided into two groups. Treatment group included 20 patients (mean age of 51 +/- 14, male/female 9/11), and the control group comprised 20 patients (mean age of 47 +/- 14, male/female 9/11). Treatment group patients were given a single dose of Devit3 ampoule (300,000 U cholecalciferol) per month orally way. Patients in the control group did not take any vitamin D for a month. The level of calcidiol was lower than normal range in two groups. After a month, treatment group patient's calcidiol increased statistically significant (6.8 +/- 3.5 to 17.8 +/- 21.4 ng/mL, p < 0.001). After a month, iPTH level decreased in the treatment group statistically significantly (368 +/- 274 to 279 +/- 179 pg/ml, p < 0.001). At the 30(th) day of the treatment, in 9/20 of the treatment group patients (45%), the iPTH value decreased at least 30% (p < 0.001). We suggest that oral depot cholecalciferol treatment causes a statistically significant decrease of serum iPTH level but does not cause a statistically significant change in Ca, P, ratio of Ca x P, or urinary calcium creatinine rate in UBD predialysis CKD. This treatment can be used safely for the predialysis CKD patients, along with the cautious control of serum calcium and phosphor.

Pseudohypoparathyroidism (PHP) is a rare inherited syndrome characterized by parathyroid hormone (PTH) resistance and is frequently associated with Albright’s hereditary osteodystrophy and resistance to other cAMP-mediated hormones. The usual neonatal presentation is mild primary hypothyroidism secondary to resistance to thyroid-stimulating hormone; hypocalcemia usually develops after age 3–5 years. This work describes the diversity in the clinical expression and course of PHP, with emphasis on calcium levels by age and treatment, in 8 children under long-term follow-up at our pediatric tertiary center. The calcium levels at presentation ranged from transient neonatal hypocalcemia to infantile hypercalcemia to childhood/adolescence hypocalcemia. Interestingly, relative hypocalciuria at diagnosis and during therapy, in the presence of renal PTH resistance, was the rule. These findings indicate that transient neonatal hypocalcemia associated with other clinical features or a family history of PHP may be a flag for clinicians to screen for PTH resistance later in life. In addition, PTH resistance may be missed by surveying calcium levels only; thus the PTH levels have to be checked as well. In addition, the recommendation for patients with hypoparathyroidism that strict low-normal calcium levels be maintained during therapy in order to prevent hypercalciuria is probably not applicable in PHP.

Renal hyperparathyroidism (rHPT) almost inevitably develops in pediatric patients with end-stage chronic kidney disease (CKD) and may require parathyroidectomy (PTX) despite intensified conservative therapy. Long-term duration of uncontrolled rHPT may result in disabling osteodystrophy and vascular calcifications. Only a few reports on children undergoing PTX for rHPT are available and mainly consist of case reports with short follow-up periods. To study this entity, we analyzed the course of 23 pediatic patients who underwent PTX for rHPT. Twenty-three patients with a mean age of 15 years and who underwent PTX for rHPT between 1986 and 2006 were evaluated. Surgical indications and techniques, specific postoperative management, and follow-up courses are described. Preoperative mean serum (s-) calcium was 2.7 ± 0.05 mmol/L (normal range = 2.2–2.7 mmol/L); s-phosphate was 1.8 ± 0.1 mmol/L (normal range = 0.8–1.6 mmol/L), and mean intact parathyroid hormone (PTH) level was 1240.1 ± 160.1 pg/ml (normal range = 11–65 pg/ml). Twenty-one patients underwent initial PTX and two patients underwent reoperative PTX. Total PTX with parathyroid autotransplantation (AT) was performed in 18 patients. In three patients less than four parathyroid glands were identified and no AT was performed consecutively. Postoperatively, no complications with respect to bleeding or vocal cord damage were recorded. The postoperative values of s-calcium, s-phosphate, and PTH decreased to or below normal range (s-calcium = 2.0 ± 0.1 mmol/L, s-phosphate = 1.2 ± 0.1 mmol/L, PTH = 50.1 ± 11.2 pg/ml). All 15 children below the age of 15 years required calcium intravenously. Follow-up was obtained in all patients 69.6 ± 11.4 months after PTX. Bone pain resolved in all previously symptomatic patients. S-calcium was 2.2 ± 0.2 mmol/L, s-phosphate was 1.4 ± 0.3 mmol/L, and PTH was 90.2 ± 21.5 pg/ml. No patient required repeated parathyroid autografting, and only one underwent an explantation of his AT six years after initial PTX. Total PTX with AT in pediatric patients with rHPT is a safe and effective procedure. It should be considered if rHPT is refractory to conservative treatment, in view of the risk of potentially lethal vascular calcifications developing in the majority of adults with childhood onset of CKD.

Congenital vascular bone syndrome (CVBS) is an abnormal enhancement or reduction of growth in long bones due to pathologic circulation during childhood. Several authors have described these clinical pictures with limb lengthening; well known are Klippel and Trenaunay and Parkes-Weber. Later, Servelle and Martorell also described cases of limb length difference, but with shortening of the pathologic limb. The mechanism of limb overgrowth is probably due to the effect of A-V shunts, while shortening occurs due to mechanical compression on bones by dysplastic vessels or flow reduction. Some molecules, like vascular endothelial growth factor and others, probably affect bone growth through a poorly understood mechanism. Diagnostically, one should try to demonstrate A-V shunts around or inside the bone or low flow vascular mass. Correction of length differences can occur spontaneously if the cause of CVBS is treated in childhood. In adults, limb length differences may be corrected by orthopaedic techniques.

Sevelamer improves hyperphosphatemia without increasing the calcium load. However, it remains unknown whether sevelamer restores bone metabolism in hemodialysis patients with low bone turnover osteodystrophy and hypoparathyroidism. We investigated the changes in serum intact parathyroid hormone (iPTH) and bone metabolic marker levels after replacing calcium carbonate with sevelamer in these patients. We also conducted stratified analysis based on patient background and multivariate analysis to determine the factors affecting these parameters. During sevelamer replacement therapy, serum calcium and phosphate concentrations, and the calcium phosphate product were measured at 0, 1, 3, and 6 months. Serum iPTH, bone alkaline phosphatase and osteocalcin concentrations were measured at 0 and 6 months. In hemodialysis patients (71 men and 46 women, 63 +/- 12 years old) serum calcium levels and the calcium phosphate product decreased significantly at 1 month. Serum iPTH, bone alkaline phosphatase and osteocalcin levels increased significantly at 6 months. Increases in serum iPTH concentrations were observed in all stratified groups. Significant increases in serum bone alkaline phosphatase and osteocalcin concentrations were found only in the relative hypoparathyroidism group (iPTH levels > or =51.5 pg/mL, the median pretreatment level). Multivariate analysis showed that the factors affecting change in serum iPTH level are baseline serum iPTH, baseline calcium level (> or =9.5 mg/dL), and dialysis duration of 10 years or longer. Sevelamer appears useful for the treatment of hyperphosphatemia in these patients. Particularly, in the relative hypoparathyroidism group, the iPTH secretory response is probably enhanced and bone turnover may have been improved as a result of reducing the calcium load.

Chronic Kidney Disease (CKD) is commonly associated with alterations in bone and mineral metabolism (renal osteodystrophy). To date, bone biopsy remains the gold standard for the diagnosis and classification of the various types of renal osteodystrophy, namely: osteitis fibrosa, mixed uremic osteodystrophy, osteomalacia, aplastic and adynamic bone disease. However, due to its invasive nature and the fact that it is quite expensive, there has been a clamor for a search for other tests. Traditionally, the level of parathyroid hormone (PTH) has been considered a surrogate of bone turnover. At this time, the search continues for a specific and sensitive biochemical marker for monitoring bone turnover in CKD., e.g., alkaline phosphatase, osteocalcin, collagen degradation products, etc. In this chapter, we also present the common radiographic findings that are commonly seen in patients with renal osteodystrophy. Other radiographic techniques such as, dual energy x-ray absorptiometry (DEXA) and deferoxamine challenge test (DFO) are also briefly discussed.

One of the major complications that arise as a result of chronic kidney disease is that of ‘renal osteodystrophy.’ It is believed to be a multifactorial disorder of altered bone modeling. Bone biopsy occupies a central role in the differentiation of the various kinds of renal osteodystrophy based on histological findings. However, due to its limitations of being a rather invasive and costly procedure, it is performed rather infrequently. Therefore, scientists started to focus on alternative measures of classifying the various types, e.g., the parathyroid hormone (PTH). PTH has been used as an indicator of bone turnover, thereby dividing the diseases into those of high turnover and low turnover. To further our understanding of this particular disease entity, a unified definition and classification was formulated and adopted by well-renowned experts from both local and international scenes, and this is presented in some detail in this chapter. It is hoped, that such unification will enhance communication, facilitate clinical decision making, and promote the evolution of evidence-based clinical practice guidelines worldwide. (2)

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.

Amelogenesis imperfecta (AI) is a collective term for a number of developmental conditions characterized by abnormal enamel formation. AI is usually not associated with generalized findings; however, a few cases of AI associated with syndromes and metabolic disorders have been reported in the literature. We report two cases of AI presenting with renal disease and thereby highlight the importance of recognizing this possible association at an early stage, as AI in some cases, may be a marker of renal disease.

Background. Cardiac calcifications are a frequent occurrence in uraemic subjects and are probably connected to the increased cardiovascular mortality of haemodialysis patients. There is substantial support to the hypothesis that low levels of serum PTH in haemodialysis patients are associated with increased vascular and cardiac calcium deposits, due to decreased buffering capacity of bone in low turnover osteodystrophy. The present study has been carried out on a cohort of patients on haemodialysis, with exclusion of previously parathyroidectomized patients, with the aim to evaluate the association between PTH serum levels and coronary calcifications. Methods. The study has been carried out in a cohort of 197 haemodialysis patients. There were 133 males and 64 females. Twenty-two patients had diabetes mellitus. Average age was 58.6 � 12.9 years. Patients were divided into groups of intact PTH levels, 0–150 (A), 150–300 (B), 300–600 (C) and >600 (D) pg/ml. Results. The values of coronary scores in the PTH groups were as follows: (A) 624.7 � 939, (B) 866.4 � 1080, (C) 1202.8 � 1742.3 and (D) 1872.7 � 2961.9. The difference between coronary calcium scores was significant (P < 0.01). A general linear model identified serum calcium and dialysis age as independent factors of calcium deposits in the high PTH group. Conclusions. No prominent association between low PTH serum levels and the severity of coronary calcium deposits in haemodialysis patients was found while increased levels of PTH, with special regard to very elevated levels, associated with more frequent hypercalcaemia and hyperphosphataemia, should be considered a major risk factor of coronary calcifications and cardiac events.

Several endocrine disorders that share resistance to PTH are grouped under the term pseudohypoparathyroidism (PHP). PHP type I, associated with blunted PTH-induced nephrogenous cAMP formation and phosphate excretion, is subdivided according to the presence or absence of additional endocrine abnormalities, Albright's hereditary osteodystrophy (AHO), and reduced Gsalpha activity caused by GNAS mutations.We sought to identify the molecular defect in four unrelated patients who were thought to have PHP-Ia because of PTH and TSH resistance and mild AHO features.Gsalpha activity and mutation analysis, and assessment of GNAS haplotype, methylation, and gene expression were performed for probands and family members.Two patients showed modest decreases in erythrocyte Gsalpha activity. Instead of Gsalpha point mutations, however, all four patients showed methylation defects of the GNAS locus, a feature previously described only for PHP-Ib. Furthermore, one patient with an isolated loss of GNAS exon A/B methylation had the 3-kb STX16 deletion frequently identified in PHP-Ib patients. In all but one of the remaining patients, haplotype analysis excluded large deletions or uniparental disomy as the cause of the observed methylation changes.Our investigations indicate that an overlap may exist between molecular and clinical features of PHP-Ia and PHP-Ib. No current mechanisms can explain the AHO-like features of our patients, some of which may not be linked to GNAS. Therefore, patients with hormone resistance and AHO-like features in whom coding Gsalpha mutations have been excluded should be evaluated for epigenetic alterations within GNAS.

Background Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC. Case presentation We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated the features of tubulointerstitial nephritis (TIN). The patient was also suspected as having primary biliary cirrhosis (PBC) because of high levels of alkaline phosphatase, IgM and the presence of anti-mitochondrial M2 antibody, though biochemical liver function was normal. Sequential liver biopsy was compatible with PBC and the diagnosis of PBC was definite. After administration of 1,25 dihydroxyvitamin D3, neutral potassium phosphate, sodium bicarbonate for osteomalacia and subsequent predonizolone for TIN, symptoms of fractures were relieved and renal function including Fanconi syndrome was ameliorated. Conclusion In this case, asymptomatic PBC was shown to induce TIN with Fanconi syndrome with dysregulation of electrolytes and vitamin D metabolism, which in turn led to osteomalacia with multiple fractures. Osteomalacia has not been recognized as a result of the renal involvement of PBC. PBC and its rare complication of TIN with Fanconi syndrome should be considered in adult patients with unexplained osteomalacia even in the absence of liver dysfunction.

We present two siblings affected with opsismodysplasia (OPS), a rare skeletal dysplasia caused by mutations in the inositol polyphosphate phosphatase-like 1 gene. The skeletal findings include short stature with postnatal onset micromelia, marked platyspondyly, squared metacarpals, delayed skeletal ossification, metaphyseal cupping, and postnatal micromelia. Respiratory compromise, delayed ambulation, and progressive lower extremity deformities are described. The severity of findings is variable. Renal phosphate wasting is associated with severe bone demineralization and a more severe phenotype. This report represents the first described cases of opsismodysplasia treated with intravenous bisphosphonate (pamidronate). Surgical management for lower extremity deformities associated with OPS is also reviewed. Level of Evidence: IV Case series

Primary hyperparathyroidism (PHPT) is currently the most common endocrine disorder in Czech Republic after diabetes and thyroid diseases particularly in postmenopausal women. Over the past 40 years PHPT has changed from a rare severe disease of the bones and kidneys to common disease with hypertension, peptic ulcer, pancreatitis, easy fatigue and proximal muscle weakness. During 43 years we have examined one of the greatest groups of patients with PHPT. In the early 1970 the estimated incidence of PHPT in former Czechoslovakia was approximately 8 cases per 100 000 persons per year. Our data showed that the incidence of PHPT increased sharply to 24 cases per 100 000 persons per year in same community with the introduction of automated serum calcium and iPTH measurement. The disease is four times more frequent in women as in man. The ratio women to men did not changed since 1981. However the incidence of PHPT changed in Czech Republic from previous years, it develops around the fifth decade of life and is increasingly discovered with advancing age. The incidence of hypertension, diabetes mellitus, cholelithiasis, pancreatitis and peptic ulcer among patients with PHPT is higher as compared with the incidence of these diseases in the general population. However there are still patients suffering from bone and renal complication of PHPT. Removing the adenoma by an experienced surgeon is the first choice of treatment of patients with PHPT. The study offers valuable data on the actual state of hyperparathyroid patients in the Czech Republic.

A 29-year-old pregnant woman with Graves’ disease presented with severe persistent hypocalcaemia after thyroidectomy. Six months prior to presentation she was diagnosed with Graves’ disease and remained uncontrolled with methimazole. She was confirmed pregnant prior to radioactive iodine ablation (RAI), and underwent total thyroidectomy during her second trimester. After surgery, continuous intravenous calcium infusion was required until delivery of the fetus allowed discontinuation at postoperative day 18, despite oral calcium and calcitriol administration. A total of 38 g of oral and 7.5 g of intravenous elemental calcium was administered. We report an unusual case of recalcitrant hypocalcaemia thought to be due to a combination of postoperative hypoparathyroidism, combined with thyrotoxic osteodystrophy and pregnancy, after surgical correction of Graves’ disease. Increased vigilance and early calcium supplementation should be a priority in the management of these patients.

Intestinal malabsorption of calcium and the development of osteomalacia in conservatively treated renal failure is explained by a quantitative deficiency of 1,25-dihydroxycholecalciferol, which also contributes to the development of hypocalcaemia. Excess of 25-hydroxycholecalciferol can substitute for this deficiency. The presence and healing of azotaemic osteomalacia is unrelated to the prevailing plasma [Ca] x [P] product. The data suggest that "vitamin D" acts directly on bone mineralisation, but the claim that this apparent effect is normally due to 25-hydroxycholecalciferol is considered unproven. Most of the phenomena of azotaemic osteodystrophy are encountered in simple vitamin D deficiency; as in that condition, deficiency of 1,25-dihydroxycholecalciferol may be of primary significance in causing secondary hyperparathyroidism in renal failure.

International audience; Pseudohypoparathyroidism (PHP) is a group of disorders characterized by end-organ resistance to the parathyroid hormone (PTH). PHP type 1A includes multihormone resistance syndrome, Albright's hereditary osteodystrophy, and obesity and is caused by mutations in GNAS exon 1 through 13. PHP type 1B (PHP1B), caused by epigenetic changes in the GNAS locus, was initially described as an isolated resistance to PTH. Epigenetic changes in GNAS have also been reported in patients who display mild Albright's hereditary osteodystrophy or mild thyroid-stimulating hormone (TSH) resistance without mutation of GNAS. Here we report a case of PHP caused by epigenetic changes in GNAS in a patient with congenital hypothyroidism. The patient was referred for a positive newborn screening for hypothyroidism (TSH 50 mIU/L). She exhibited severe clinical features of congenital hypothyroidism. The thyroid was in place, and etiologic explorations were negative. TSH was normalized under L-thyroxin, and the symptoms disappeared, except for a macroglossia. In childhood, PHP was suspected in addition to elevated PTH, obesity, brachydactyly, and a rounded face. Sequencing, methylation analysis, and large deletion research were performed in GNAS. No genetic mutations were found. Methylation analysis revealed a broad epigenetic defect without deletion in GNAS consistent with sporadic PHP1B. The multilocus methylation analysis were negative. This finding expands the known onsets of PHP1B and emphasizes the need for a new PHP classification system. This case report has important consequences for the etiologic diagnosis of congenital hypothyroidism because it adds a new cause of the disease.

The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73m(2). 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. KFH Foundation for Preventive Medicine European Renal Association-European Dialysis and Transplant Association Federal Ministry of Education & Research (BMBF) (01EO0802) Pfizer Deutschland GmbH Kidney Research UK (KRUK) (RP39/2013)

The disruption of multiorgan systems biology produced by renal injury in early stages of kidney injury and disease was unrecognized until its elucidation during the investigation of the chronic kidney disease-mineral bone disorder (CKD-MBD). The disordered systems biology causes the CKD-MBD and contributes to major components of increased cardiovascular risk for CKD patients. The result, in addition to the previously recognized renal osteodystrophy, is increased cardiovascular mortality in CKD. The inception of the CKD-MBD was only recently realized to begin with the early effects of kidney disease, and its pathophysiology involves circulating factors produced by renal repair and newly discovered hormones, such as FGF23 and cut klotho. Progressing from its inception, the disruption of the multiorgan system leads to the pathophysiology previously recognized as secondary hyperparathyroidism, hyperphosphatemia, calcitriol deficiency, and renal osteodystrophy that are now incorporated into the CKD-MBD syndrome.

Albright hereditary osteodystrophy (AHO) is a congenital disorder caused by heterozygous loss-of-function mutations of the GNAS gene encoding Gsα, the ubiquitously expressed G protein α-subunit that is required for intracellular cAMP generation in response to hormones and other extracellular signals. AHO patients develop short stature, brachydactyly, subcutaneous ossifications, and, in some cases, neurocognitive impairment. Due to genomic imprinting of GNAS, mutations on the maternal allele also lead to multihormone resistance and early-onset obesity, a condition known as pseudohypoparathyroidism type 1a. In contrast paternal mutations only lead to AHO, also known as pseudopseudohypoparathyroidism. In some instances, the same Gsα mutations are associated with a more severe form of ectopic ossification known as progressive osseous heteroplasia.

Urolithiasis is a common disease with the lifetime prevalence estimated to be between 10 and 15 % [19, 53]. Patients with congenital urologic disorders such as myelomeningocele (MMC), bladder exstrophy, and posterior urethral valves (PUV) represent a special population with regard to urolithiasis. These patients are at an increased risk of stone formation due to a variety of reasons including: bladder dysfunction, urinary tract reconstruction, urinary tract infections (UTIs), obesity, and osteodystrophy.

Constitutional disorders of bone, commonly termed skeletal dysplasias (SDs), are inherited disorders of cartilage and/or bone that affect their growth, morphometry and integrity. Associated skeletal abnormalities are usually but not invariably symmetrical. They may be classified as osteochondrodysplasias, which are conditions associated with abnormalities of the growth (dysplasias) or texture (osteodystrophy) of bone and/or cartilage, or dysostoses, which are conditions secondary to abnormal blastogenesis (occurring at or around the 6th week of in utero life). Skeletal involvement may also occur in other multisystem hereditary and acquired syndromes. The 2010 Nosology and Classification of Genetic Skeletal Disorders listed 456 conditions, of which approximately 50 are perinatally lethal, and 316 are associated with one or more of 226 genes. When an SD is suspected, a standard series of radiographs, collectively known as a skeletal survey, should be performed. The diagnosis of individual conditions is highly dependent on radiographic pattern recognition, which is achieved through a systematic review of the images and enhanced by discussion with colleagues and through the use of available tools, such as atlases and digital databases. This article summarises a systematic approach to the diagnosis of SDs, demonstrated using examples of some of the more common lethal and non-lethal conditions.

Background Vascular access (VA) for hemodialysis (HD) is crucial for the course of treatment and a good prognosis for patients. There have been numerous investigations of the influence of homocysteine (Hcy) on VA complications, but to date the role of Hcy is controversial. The present study of HD patients was designed to investigate the relationship between previous VA failure (VAF) and the serum level of Hcy and other routinely measured biochemical parameters. Patients and Methods Eighty-five patients participated in the study. Their mean age was 62 years, and their mean duration on HD treatment was 33 months. Incidence of VAF over the preceding 18 months was analyzed retrospectively. VAF was defined as any dysfunction of VA that required a different surgical intervention. Serum levels of Hcy and several other biochemical parameters related to the adequacy of HD, osteodystrophy, nutrition status, and atherosclerosis were determined. In addition, body mass index, normalized protein catabolic rate, and mean blood pressure were calculated. Additionally, the serum level of Hcy was determined in a healthy control group (n=12). Results VAF, as venous or graft thrombosis (n=12) and stenosis of anastomosis (n=13), was observed in 25 of the HD patients (30%). Mean Hcy level was significantly higher in the HD patients than in the control group (26.8±9.5 vs. 11.8±2.9 μmol/L, p

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.

A heifer with developmental skeletal disorder was presented to the ruminant clinic of the University of Berne. Abnormal long bone growth and a wobbling gait were the main clinical signs. All long bones were examined radiologically, several parameters of body size were measured and the results were compared to the measurements of a healthy control animal. Haematology and blood chemistry were normal. Based on the poor prognosis the animal was slaughtered. The final diagnosis of hyena disease was based on the characteristic growth disturbances in the caudal parts of the body, giving the animal a hyena-like appearance. For the first time a case of hyena disease is reported in Switzerland.

Global gene expression profiling has been used to study the molecular mechanisms of increased bone remodeling caused by PHPT. This disease is a model for chronic over-stimulation of target organs by PTH due to an inappropriate overproduction of the hormone. Hyperactivity of osteoblasts and osteoclasts lead to increased calcium and phosphate mobilization from the skeleton and hypercalcaemia. The ensemble of genes that alter expression and thus is responsible for the effects of chronic PTH stimulation is today largely unknown. The differentiated gene expression profiles revealed characteristic molecular disease modalities which define the bone remodeling abnormalities occurring in PTH dependent osteodystrophy. We analyzed mRNAs in transiliacal bone biopsies from 7 patients with PHPT using Affymetrix HG-U133A Gene Chips containing more than 22000 different probe sets. Similar analyses of the global transcriptional activity were repeated in a second bone biopsy from the same patient taken one year after surgery and reversal of disease parameters. Real time PCR was carried out on many genes for corroboration of the results. Out of more than 14500 different genes examined, 99 which were related to bone and extra-cellular matrix, showed altered expression. Of these were 85 up- and 14 down-regulated before operation. The majority of regulated genes represented structural and adhesion proteins, but included also proteases and protease regulators which promote resorption. Increased expressions of collagen type 1 and osteocalcin mRNAs in disease reflecting the PTH anabolic action were paralleled by increased concentrations of these proteins in serum. In addition, genes encoding transcriptional factors and their regulators as well as cellular signal molecules were up-regulated during disease. The identified genetic signature represents the first extensive description of the ensemble of bone and matrix related mRNAs, which are regulated by chronic PTH action. These results identify the molecular basis for this skeletal disease, and provide new insight into this clinical condition with potential bearing on future treatment.

Background. Bone loss remains a serious problem after kidney transplantation and is most pronounced during the first months after engraftment. Bisphosphonates are frequently used to treat posttransplant osteodystrophy, but data of large randomized controlled trials (RCTs) are missing. Methods. We, therefore, conducted this systematic review of the literature, searching electronical databases, reference lists and abstracts from scientific meetings to identify RCTs in all languages. The primary outcome assessed was the change in bone mineral density (BMD) during the early posttransplantation period. Based on the mean BMD change presented in the identified publications, the authors were asked for the individual BMD results of all randomized patients, determined at lumbar spine and femoral neck before and after bisphosphonate therapy. Data were pooled for summary estimates by using weighted mean differences of absolute change in BMD. An analysis of covariance was performed, adjusted for individual baseline values, treatment arm and individual trial. Results. Five studies involving 180 participants were included in our meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing post-transplant osteodystrophy. BMD decline at the lumbar spine within 6–12 months after transplantation was significantly reduced by 0.06 g/cm 2 in patients treated with bisphosphonates (95% CI 0.05–0.08 g/cm 2 ). At the femoral neck, the loss of BMD was reduced by 0.05 g/cm 2 during this period (95% CI 0.0–0.11 g/cm 2 ), reaching just non-statistical significance. This benefit of bone loss prevention could be reached without major side effects. Conclusion. Bisphosphonates are effective in preventing bone loss in the early post-transplant period.

Objective: To review the literature on the safety and efficacy of lanthanum carbonate for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). Data Sources: Primary literature was obtained through a PubMed search (1966–September 2005) using the key terms Fosrenol and lanthanum carbonate. The FDA review, manufacturer-provided data, and published abstracts on lanthanum carbonate were also reviewed and evaluated. Study Selection and Data Extraction: Human studies in which lanthanum carbonate was compared with placebo or active control for the treatment of hyperphosphatemia secondary to renal disease were included. Dose-titration studies were excluded. Data Synthesis: Phosphate-lowering agents and dietary phosphate restriction are currently the first-line therapies for initial treatment of hyperphosphatemia associated with ESRD. Lanthanum carbonate is a highly effective non–aluminum, non–calcium-containing phosphate binder. It is the only FDA-approved phosphate binder that is available as an unflavored chewable tablet that may be taken without water. Conclusions: Clinical studies demonstrate that lanthanum carbonate is more effective than placebo but as or less effective than standard therapies in lowering serum phosphate to target levels. When compared with calcium salts, lanthanum carbonate had a lower incidence of hypercalcemia and a lower risk of patients developing bone disease. However, in clinical trials, patients receiving lanthanum carbonate had greater discontinuation rates, some due to adverse events. The long-term safety data (>5 y), including the potential for lanthanum accumulation in the bone with subsequent development of osteodystrophy, remain unknown.

Albright's hereditary osteodystrophy is a rare inherited metabolic disorder characterized by a typical phenotype. It may be associated with or without resistance to parathyroid hormone (pseudohypoparathyroidism). Both forms may co-exist in the same family. Pseudohypoparathyroidism Type 1 and Pseudo-pseudohypoparathyroidism occur as a consequence of reduced erythrocyte membrane coupled with Gs alpha activity. We report here the variable inheritance of hormone resistance in the presence of characteristic phenotype and reduced Gs alpha activity in the same family.

Klinefelter's syndrome is rarely associated with hypocalcemia, especially pseudohypoparathyroidism (PHP) type Ib. We describe a case of Klinefelter's syndrome associated with seizure, PHP type Ib and multiple endocrine dysfunctions. A 19-year-old Taiwanese male was admitted due to seizures with loss of consciousness. He had been diagnosed with Klinefelter's syndrome with seizure disorder and hypocalcemia 3 months previously. Physical examination revealed eunuchoidism but no osteodystrophy, while laboratory data revealed severe hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone. Chromosomal study showed 47, XXY. Osteoporosis was found on chest and abdominal radiography. Dense calcification in the cerebrum and cerebellum was shown on brain computed tomography and magnetic resonance imaging. Elevation of the patient's serum calcium level was noted after vitamin D and calcium carbonate supplements were given. Klinefelter's syndrome is rarely associated with PHP type Ib; our patient's hypocalcemia improved after long-term aggressive treatment.

Background Uremic patients on regular dialytic treatment (RDT) are often affected by a complex metabolic syndrome leading to osteodystrophy. Bone changes are primarily due to high bone turn over, often combined with a mineralization defect leading to increased bone fractures and bone deformities. Although rarely considered, the craniofacial skeleton represents one of the peculiar targets of this complex metabolic disease whose more dramatic pattern is a form of leontiasis ossea. This complication, although described, has never been evaluated in depth nor quantitatively assessed. In order to assess facial deformities in uremic conditions and to understand the possible relation with hyperparathyroidism, we undertook a quantitative evaluation of soft facial structures in a cohort of uremic patients undergoing RDT. Methods The three-dimensional coordinates of 50 soft-tissue facial landmarks were obtained by an electromagnetic digitizer in 10 male and 10 female patients with chronic renal insufficiency aged 53–81 years, and in 34 healthy individuals of the same age, ethnicity and sex. Uremic patients were enrolled according to hyperparathyroid status (PTH < 300 pg/mL and PTH > 500 pg/mL). From the landmarks, facial distances, angles and volumes were calculated according to a geometrical face model. Results Overall, the uremic patients had significantly larger facial volumes than the reference subjects. The effect was particularly evident in the facial middle third (maxilla), leading to an inversion of the mandibular-maxillary ratio. Facial dimensions were increased in all three spatial directions: width (skull base, mandible, nose), length (nose, mandible), and depth (mid face, mandible). The larger maxilla was accompanied by a tendency to more prominent lips (reduced interlabial angle). Some of the facial modifications (nose, lips, mandible) were significantly related to the clinical characteristics of the patients (age, duration of renal insufficiency and PTH levels). Conclusions This report, the first in the literature, shows that facial structures of uremic patients are enlarged in comparison with matched normal subjects and that increased bone turnover could be responsible – at least in part – for facial bone changes.

Pseudohypoparathyroidism (PHP) type Ia is characterized by hypocalcemia due to PTH resistance and by features of Albright's hereditary osteodystrophy, including short stature, obesity, subcutaneous calcification and brachydactyly. A wide variety of clinical and biochemical manifestations have been reported. We report two cases of PHP type Ia in duozygotic twins with different phenotypes. The proband was a 10-yr-old girl. She showed subcutaneous ossification, shortening of the metacarpal bone, short stature, obesity and round face. She had normocalcemia (8.9 mg/dl), high-normal phosphate (5.0 mg/dl) and increased levels of serum intact PTH (152 pg/ml) and TSH (9.17 μIU/ml) levels. Her twin younger brother had atypical Albright's hereditary osteodystrophy with only mild obesity and subcutaneous calcifications, but he showed a low level of serum calcium (7.0 mg/dl) and high levels of serum phosphate (7.6 mg/dl), intact PTH (377 pg/ml) and TSH (6.9 μIU/ml). We diagnosed them as having PHP type Ia on the basis of clinical and biochemical findings, Ellsworth-Howard test and family history. There is considerable variability in clinical and biochemical features of PHP type Ia even among affected duozygotic twins. The differences of intrauterine environment and growth history cannot account for the variable phenotypes of PHP type Ia. Even if a patient shows no AHO features, examination of all family members should be undertaken.

The aim of the present study was to evaluate the presence of pathological alterations attributable to vitamin deficiency in osteological remains from the church of St. Pierre in Puy de St. Pierre, Briancon, France. We recorded alterations referable to scurvy, an acquired osteodystrophy due to vitamin C deficiency, which causes both skeletal and vascular lesions in humans. Scurvy presents a different clinical picture in children and adults: in the latter, in leaves skeletal signs on the palate and teeth. The recording of osteodystrophies attributable to vitamin deficiency allowed us to make general inferences about the nutritional profile of the group under study. The study of this pathology, as well as that of nutritional stresses, can be related to the geographical-environmental conditions of the population to which the sample belongs. This is important from the anthropological point of view, especially in order to examine alimentary habits within the context of the man-environments relationship.

Background Paricalcitol, a vitamin D analog, is commonly administered three times weekly to control secondary hyperparathyroidism in hemodialysis patients. Less frequent dosing would be more convenient, require less nursing time, and be an option in other dialysis modalities. No studies have examined the efficacy of once-weekly dosing of paricalcitol. Methods Chronic hemodialysis patients receiving a stable dose of paricalcitol three times weekly with intact PTH (iPTH) 100-500 ng/l were monitored during a two-week baseline, then were converted to a single mid-week paricalcitol dose equal to the previous cumulative weekly dose. Serum calcium and phosphorus were monitored weekly and iPTH levels determined during study Weeks 4 and 8. A single paricalcitol dose adjustment was made during study Week 5 based on iPTH to achieve a target value of 150-300 ng/l. Phosphate binders and calcium dialysate bath were kept constant during the study. Results In the 25 patients, mean iPTH was 295 +/- 107 ng/l at baseline, and not significantly different at Week 4 (307 +/- 111 ng/l) or Week 8 (285 +/- 98 ng/l). Paricalcitol dose increases mid-study were almost exclusively in patients with iPTH > 300 ng/l. Calcium, phosphorus, and calcium x phosphorus product were not significantly different on weekly therapy. (Only one patient developed a calcium > 2.55 mmol/l during the study.) Conclusion Once-weekly dosing of paricalcitol is an effective option in treatment of secondary hyperparathyroidism. Less frequent dosing may better allocate nursing time and potentially benefit other patient populations with CKD and ESRD.

Transplanted patients experience rapid loss of bone, high fracture rates, and increases in morbidity and mortality as a consequence of a posttransplant scenario that is highly deleterious to the skeleton. Immune suppressive drugs, especially glucocorticoids, are toxic to bone, often acting on a background of preexisting osteodystrophy resulting from long-standing renal, hepatic, cardiac, or pulmonary disease. Cyclosporin and tacrolimus lead to a severe osteopenic state in rats, but the skeletal toxicity of the calcineurin inhibitors in the clinical environment is less clear. Nor is it clear whether cyclosporin and tacrolimus differ in their skeletal actions. Mycophenolate mofetil and sirolimus do not appear to have important skeletal toxicity. Preventative strategies include minimizing glucocorticoid exposure and implementing therapies to counter the increase in bone resorption and decrease in bone formation that follows transplantation. Antiresorptive agents, especially bisphosphonates, appear capable of retarding or halting the early bone loss and possibly reduce fracture rates also. Vitamin D and calcium are ineffective, but calcitriol has utility in some reports. Bone anabolic agents, such as synthetic parathyroid hormone and growth hormone, have potential, but data are lacking.

Calciphylaxis (calcific uremic arteriolopathy) is a vasculopathy that is often defined in patients due to renal failure, however, some patients with calciphylaxis do not show secondary or tertiary hyperparathyroidism. It results from mural calcification of arteries and arterioles in the deep dermis and subcutaneous adipose tissue, leading to vessel occlusion. The resulting ischemia may be so severe that infarction of the downstream tissue may develop, the most affected sites being the skin and subcutaneous adipose tissue. The regions of the body with thicker subcutaneous adipose tissue such as the breast, abdomen, thighs and buttocks may be more frequently affected. 1 The accepted concept is that reduced glomeruler filtration rate, even in the early stages of end-stage renal disease (ESRD), results in diminished renal phosphorus excretion and an increase in serum phosphorus concentration. The retained inorganic phosphorus combines with plasma calcium and the calcium × phosphate product with CaHPO4 concentration rise. 2 This leads to the stimulation of parathyroid hormone secretion and secondary hyperparathyroidism as well as the resorption of calcium and phosphorus from bone with resulting osteodystrophy and metastatic calcification. Cutaneous metastatic calcification was reported as long ago as 100 years. The lesions are quite characteristic, starting as areas of painful purple discoloration in the extremities that are plaquelike or nodular. They usually progress to necrotizing gangrenous areas and ulcerations. Some reports describe actual gangrene and self-amputation of digits or extremities. 3 In this case report, we present an 8-year-old girl who experienced cutaneous and widespread visceral calcifications due to poor compliance of her parents to the treatment of chronic renal failure. Case report