Hypophosphatemic rickets: results of a long-term follow-up

This study reports the benefits and side effects of conventional treatment, phosphate and calcitriol supplementation in patients with heritable hypophosphatemic rickets and a long-term follow-up, median of 60.9 months. The group is composed of 17 patients (ten girls). Sixteen patients presented with bone pain and/or deformities, and in one patient the diagnosis was radiological. All the patients had increased alkaline phosphatase, hypophosphatemia, decreased fractional phosphate tubular reabsorption (TRP) and maximum tubular phosphate reabsorption/glomerular filtration rate ratio (TPO4/GFR). Ten of 17 patients had metabolic acidosis, which was corrected only with the conventional treatment. Potassium citrate was prescribed to the patients who developed hypercalciuria. Excluding one patient with pulmonary dysfunction, the remaining 16 patients were divided into two groups according to the age at treatment onset (T0): group I (GI) 4 years (n =9) and GII <4 years (n =7). GI and GII had similar follow-up periods and treatment protocols. Seven out of nine GI patients underwent orthopedic surgery, in contrast to none of GII. Anthropometric data results showed that within each group there is no difference in weight and stature z -score at T0 and at the end of the observation (Tf), but, when both groups are compared, GII shows higher z -score for stature at T0 (p <0.05) and at Tf (p <0.05). Nephrocalcinosis developed in three cases and correlated with hypercalciuria (p <0.001) and dose of calcitriol (p =0.03). In conclusion, higher stature z -score is associated with early treatment. A careful protocol is recommended to detect such complications as nephrocalcinosis. We suggest potassium citrate for patients with hypercalciuria to avoid calcium precipitation.     

Hypophosphatemic rickets: the role of hemiepiphysiodesis

Despite early medical intervention, children with hypophosphatemic rickets often have progressive deformities in the lower extremities. With the forces imparted by gravity and weight bearing, varus or valgus deformities that might otherwise have been physiological are likely to progress, causing gait disturbance and pain. Proper medical management is important and may theoretically slow or prevent the progression of varus or valgus, but is ineffective at correcting deformity once established. We have reviewed the literature and gathered a series of 10 patients, most of whom underwent hemiepiphysiodesis. We are presenting the rationale for, and the results of, that surgery, in an effort to define the role of this minimally invasive procedure.     

Hypophosphatemic rickets due to perturbations in renal tubular function

The common denominator for all types of rickets is hypophosphatemia, leading to inadequate supply of the mineral to the growing bone. Hypophosphatemia can result from insufficient uptake of the mineral from the gut or its disproportionate losses in the kidney, the latter being caused by either tubular abnormalities per se or the effect on the tubule of circulating factors like fibroblast growth factor-23 and parathyroid hormone (PTH). High serum levels of the latter result in most cases from abnormalities in vitamin D metabolism which lead to decreased calcium absorption in the gut and hypocalcemia, triggering PTH secretion. Rickets is a disorder of the growth plate and hence pediatric by definition. However, it is important to recognize that the effect of hypophosphatemia on other parts of the skeleton results in osteomalacia in both children and adults. This review addresses the etiology, pathophysiologic mechanisms, clinical manifestations and treatment of entities associated with hypophosphatemic rickets due to perturbations in renal tubular function.     

Hypophosphatemic rickets presenting as recurring pedal stress fractures in a middle-aged woman.

Stress fractures frequently occur from overtraining. When stress fractures recur, underlying metabolic abnormalities should be ruled out. We report a middle-aged woman in whom such an evaluation demonstrated previously undiagnosed hypophosphatemic rickets after she presented with recurring stress fractures in her feet. Treatment with phosphate and calcitriol was associated with clinical improvement that would likely not have occurred without this intervention. Any patient with recurring stress fractures should be evaluated with several screening laboratory tests, metabolic bone x-rays, and a measurement of bone mineral density.     

Hypophosphatemic rickets accompanying McCune-Albright syndrome: evidence that a humoral factor causes hypophosphatemia

McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia. However, it remains unclear whether a humoral factor is associated with the cause of hypophosphatemia. We isolated cells with mutations of the Gsalpha gene from fibrous bone dysplasia tissues of two MAS patients (MAS cells). Severe combined immunodeficiency (SCID) mice were subjected to experiments using from one of these cells patients. Effects of conditioned media (CM) isolated from MAS cells (MAS-CM) on phosphate transport were investigated by using rat renal slices, the renal cell line OK-B, rat intestinal rings and the human intestinal cell line Caco-2. In addition, the effects of MAS-CM on human sodium-dependent phosphate transporter (NPT2) gene promoter activity expression were investigated in the renal cell line OK-B2400 and were compared with the effects of CM isolated from a patient with oncogenic hypophosphatemic osteomalacia (OHO). MAS cells caused significant hypophosphatemia (P < 0.05) and elevated serum alkaline phosphatase activity (P < 0.05) in SCID mice. The MAS-CM significantly inhibited phosphate uptake in everted intestinal rings (P < 0.01), whereas it had no effect on glucose uptake. The MAS-CM had no effect on either phosphate uptake in the kidney or NPT2 gene promoter activity. In contrast, the CM of the OHO patient significantly inhibited phosphate uptake and NPT2 gene promoter activity. These results indicate that the humoral factor derived from fibrous dysplasia cells of the MAS patient is different to that from OHO patients, because the humoral factor from the MAS patient inhibited phosphate transport not in the kidney but in the intestine.     

Hyperosmolality due to antacid treatment

Magnesium trisilicate mixture is an antacid used commonly in our Intensive Care Unit in the prevention and treatment of stress ulcers. In this case the administration of large doses over a period of time led to the development of massive hyperosmolality, cerebral dehydration and coma. Management with hypotonic fluid resulted in complete recovery.     

Hypophosphatemic rickets is associated with disruption of mineral orientation at the nanoscale in the flat scapula bones of rachitic mice with development

Metabolic bone disorders such as rickets are associated with altered in vivo muscular force distributions on the skeletal system. During development, these altered forces can potentially affect the spatial and temporal dynamics of mineralised tissue formation, but the exact mechanisms are not known. Here we have used a murine model of hypophosphatemic rickets (Hpr) to study the development of the mineralised nanostructure in the intramembranously ossifying scapulae (shoulder bone). Using position-resolved scanning small angle X-ray scattering (SAXS), we quantified the degree and direction of mineral nanocrystallite alignment over the width of the scapulae, from the load bearing lateral border (LB) regions to the intermediate infraspinous fossa (IF) tissue. These measurements revealed a significant (p<0.05) increase in mineral nanocrystallite alignment in the LB when compared to the IF region, with increased tissue maturation in wild-type mice; this was absent in mice with rickets. The crystallites were more closely aligned to the macroscopic bone boundary in the LB when compared to the IF region in both wild type and Hpr mice, but the degree of alignment was reduced in Hpr mice. These findings are consistent with a correlation between the nanocrystallites within fibrils and in vivo muscular forces. Thus our results indicate a relevant mechanism for the observed increased macroscopic deformability in rickets, via a significant alteration in the mineral particle alignment, which is mediated by an altered spatial distribution of muscle forces.     

Genetic renal disorders with hypomagnesemia and hypocalciuria

The combination of hypomagnesemia and hypocalciuria is the phenotypic signature of two distinct genetic renal tubular transport disorders: Gitelman's syndrome and autosomal dominant isolated renal magnesium wasting. In the past 5 years the genetic defects underlying these disorders have been elucidated through positional candidate cloning approaches. The defective proteins involved in both diseases are located within the distal convoluted tubule (DCT), a segment of the nephron known to play an important role in active magnesium reabsorption in the nephron. The introduction outlines the magnesium handling in the body in general and, in particular, in the kidney, followed by a detailed discussion of Gitelman's syndrome and isolated renal magnesium wasting, including the clinical and biochemical symptoms, genetic aspects and pathophysiology.     

阿德福韦酯治疗慢性乙型肝炎致低磷性骨软化症8例

目的：进一步探讨阿德福韦酯（ADV）所致低磷性骨软化症的临床特点。方法回顾性分析2010至2012年共收治的8例慢性乙型肝炎患者经ADV治疗所致低磷性骨软化症的临床表现、治疗和转归。结果8例患者均在服用ADV后出现低磷血症及骨质疏松,其主要临床表现为乏力、多发骨痛,进行加重至行走障碍;低血磷、低尿酸和高碱性磷酸酶血症、骨密度检查提示骨质疏松。经停用ADV、对症补钙、补磷治疗后患者的血磷恢复正常,疼痛缓解,骨质疏松改善。结论 ADV可引起低磷性骨软化症;补充磷、维生素D3及钙剂治疗可恢复。     

Serum-aluminum in nondialyzed chronic uremic patients before and during treatment with aluminum-containing phosphate-binding gels

Se-aluminum was measured in a study group and a control group of undialyzed chronic uremic patients having a similar reduction of kidney function (median GFR 7 [range 5-15] ml/min/1.73 m2). Se-aluminum values (0-11, median 3, micrograms/l) in the control group (31 patients) receiving no treatment with aluminum-containing phosphate-binding gels, were all below the upper normal range (17 micrograms/l). The study group (28 patients) was treated with oral Al(OH)3 for 0.5-18 (median 6) months. Se-aluminum in this group was 17-230 (median 35) micrograms/l. It is concluded that se-aluminum increases in undialyzed chronic uremic patients ingesting aluminum-containing antacids. The study suggests that se-aluminum varies with the daily dose of aluminum hydroxide, and that se-aluminum in particular increases when the daily doses are more than 3 g Al(OH)3.