Long-Term Influence of Calcitriol (1,25-Dihydroxyvitamin D) and Supplemental Phosphate in X-Linked Hypophosphatemic Rickets

PEDIATRICS ◽  
1983 ◽  
Vol 71 (4) ◽  
pp. 559-567 ◽  
Author(s):  
Russell W. Chesney ◽  
Richard B. Mazess ◽  
Philip Rose ◽  
Alan J. Hamstra ◽  
Hector F. DeLuca ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Statistical Significance ◽  
Urinary Calcium ◽  
Hypophosphatemic Rickets ◽  
Calcium Excretion ◽  
Vitamin D2 ◽  
Photon Absorptiometry ◽  
Dihydroxyvitamin D ◽  
Familial Form

Ten patients with hypophosphatemic rickets (eight with X-linked familial form) were treated with vitamin D2 (10,000 to 75,000 units per day) and oral phosphate (1.5 to 3.6 gm) for a total of 438 treatment months. Therapy was then changed to calcitriol (17 to 34 ng/kg/day) and the same phosphate dose. Patients served as their own controls, and significant biochemical changes noted were an increase in immunoreactive parathyroid hormone from 29 ± 9 (SD) µlEq/ml (pre-phosphate) to 62 ± 34 on vitamin D2 plus PO4, then decreasing to 40 ± 20 on a regimen of 1,25-dthydroxyvitamin D (1,25(OH)2D) plus PO4; serum PO4 rose from 2.44 ± 0.45 (SD) mg/100 ml to 3.06 ± 0.79 and then to 3.43 ± 0.76; alkaline phosphatase activity decreased from 677 ± 298 (SD) UI/liter to 457 ± 183 to 290 ± 176. Serum calcium and creatinine levels were unchanged. Both urinary calcium excretion and caicium-creatinine ratio decreased after therapy with 1,25(OH)2D. Urinary phosphate excretion was higher after calcitriol administration. Serum 1,25(OH)2D levels were low in these vitamin D2-treated patients, and an inverse relationship between serum 25(OH)D and 1,25(OH)2D was found. Improved bone mineralization was evident from serial assessment by photon absorptiometry, and radial bone mineral content rose from 75.3% ± 2.2% of expected to 82.2% ± 1.4% (P < .005). Stature was improved when assessed by standard deviation for chronologic age but did not reach statistical significance. Long-term 1,25(OH)2D plus phosphate therapy appears to be more efficacious than vitamin D2 in this form of rickets, particularly in improving phosphate homeostasis.

scholarly journals Hypercalcemia Due to Immobilization

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A196-A196
Author(s):  
Irshad Ahamed ◽  
Niyati Jauhar
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spinal Cord Injuries ◽  
Bone Mineralization ◽  
Weight Bearing ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Underlying Malignancy

Abstract Background: Hypercalcemia associated with immobilization is an infrequent diagnosis. It is usually associated with prolonged immobility due to traumatic brain injury or spinal cord injuries. It results from rapid bone turnover. Diagnosis requires workup to rule out other causes of hypercalcemia. Keywords: Hypercalcemia; immobilizationCASE REPORT: We report a case of a 49 year old woman with severe traumatic brain injury and paraplegia following an electric-scooter accident. She had an extended stay in hospital and was noted to be hypercalcemic after six months’ in-patient. Laboratory investigations showed increased calcium level at 3.34 mmol/l (ref. 2.15–2.50 mmol/l) with diminished parathyroid hormone (PTH) level of 0.2 pmol/l (ref. 1.6–6.9 pmol/l), low 25-hydroxyvitamin D at 26.7 ug/l (toxicity >100 ug/l) and low 1,25-dihydroxyvitamin D at 13 pg/l (ref. 18–78 pg/l) with increased 24-H urinary calcium at 11.74 mmol/day (ref. 2.50 – 7.50 mmol/day). There was no clinical or biochemical evidence of other endocrinopathies such as hyperthyroidism or adrenal insufficiency. There was also no underlying malignancy to explain the hypercalcemia. In the context of recent prolonged immobility, a diagnosis of immobilisation hypercalcemia (IH) was made. The pathophysiology of IH is unclear. It is said that muscle activity transmits signal for bone formation through osteocytes and with immobility, mechanical stimulation is reduced, causing unopposed resorption. Another cause may be increased acidic environment due to low blood flow which impairs bone mineralization. There is also increased osteoclastic resorption, leading to loss of calcium from bones and hypercalciuria. Hypercalcemia occurs when calcium efflux from bone exceeds renal calcium excretion. For our patient, hydration therapy was initiated with no improvement in calcium. SC calcitonin was added and IV pamidronate given. Two weeks after treatment serum calcium improved to 2.38 mmol/L and remained normal on subsequent monitoring. Conclusion: IH is a known but uncommonly recognized complication in immobile patients. If not treated properly patients may develop typical complications of hypercalcemia including dehydration, confusion and renal impairment. Mobilization by using weight bearing exercises where possible is a cornerstone of long term management. In conclusion, our case serves as an important reminder of this differential and illustrates the management of IH.

Effects of Hydrochlorothiazide and Amiloride in Renal Hypophosphatemic Rickets

PEDIATRICS ◽  
1985 ◽  
Vol 75 (4) ◽  
pp. 754-763
Author(s):  
Uri Alon ◽  
James C. M. Chan
Keyword(s):  
Control Period ◽  
Fractional Excretion ◽  
Urinary Calcium ◽  
Serum Phosphate ◽  
Phosphate Concentration ◽  
Hypophosphatemic Rickets ◽  
Calcium Excretion ◽  
To Receive ◽  
Phosphate Supplementation

The effects of thiazide diuretics on serum phosphate concentration, renal tubular threshold for phosphate, and urinary calcium excretion in children with renal hypophosphatemic rickets were studied. There were nine controlled acute studies conducted in five patients, and, in addition, seven long-term studies of up to 26 months were performed. During the acute studies, the children continued to receive the same doses of oral calcitriol and phosphate supplementation as at home. Hydrochlorothiazide, 1.50 to 2.25 mg/kg/d, was used alone in the first four studies; hydrochlorothiazide and amiloride at a dose of 1 mg for each 5 mg of hydrochlorothiazide were used in the other five studies. Administration of the diuretics for four days gave rise to a significant increase in serum phosphate concentration from 3.1 ± 0.4 mg/dL to 3.7 ± 0.9 mg/dL (P < .01) and in tubular threshold for phosphate from 1.31 ± 0.45 mg/dL to 1.74 ± 0.60 mg/dL (P < .01). These changes were accompanied by significant reductions in urinary sodium excretion from 135 ± 39 mEq/24 h during the control period to 99 ±42 mEq/24 h on the fourth day of therapy (P < .05), fractional sodium excretion from 0.99% ± 0.42% to 0.81% ± 0.42% (P < .05), and urinary calcium excretion from 57.3 ± 28.9 mg/24 h to 19.0 ± 13.1 mg/24 h (P < .01). Fractional excretion of phosphate divided by fractional excretion of sodium after the treatment with diuretics was not significantly different from that observed at the end of the control period. Increments in serum phosphate concentrations were correlated with elevations in serum albumin concentrations (r = .739; P <.02). As an additional index of intravascular volume contraction, the elevations in serum phosphate concentrations were correlated with the increase in BUN, (r = .793; P < .01). The addition of amiloride in the last five studies prevented the hypokalemia and alkalosis that had complicated the administration of hydrochlorothiazide. Long-term follow-up studies for a total of 119 therapy-months on six children and one adult, who continued to receive the diuretics concomitantly with calcitriol and phosphate supplementation, showed that they were free of complications except for a transient episode of hypercalcemia and hypercalciuria in one patient. In comparison with the previous period of treatment with calcitriol and phosphate without diuretics, linear growth velocity and healing of the rickets were not changed in two children and improved in the other four after the addition of hydrochlorothiazide and amiloride. Three patients who previously had hypercalciuria responded to thiazide administration by reverting to and maintaining normocalciuria. Ultrasonography showed no nephrocalcinosis throught the period of diuretic treatment of up to 3 years. It is concluded that some patients with renal hypophosphatemic rickets can benefit from the adjunct diuretic therapy by reducing the requirements for the large doses of phosphate supplementation and by providing a wider margin of safety for the currently accepted mode of therapy.

Renal Hypophosphatemic Rickets: Growth Acceleration After Long-Term Treatment with 1,25-Dihydroxyvitamin-D3

PEDIATRICS ◽  
1980 ◽  
Vol 66 (3) ◽  
pp. 445-454 ◽  
Author(s):  
James C. M. Chan ◽  
Robert D. Lovinger ◽  
Peter Mamunes
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Bone Age ◽  
Term Treatment ◽  
Hypophosphatemic Rickets ◽  
Phosphorus Concentration ◽  
Calcium Excretion ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Long Term Treatment

Treatment with 1,25-dihydroxyvitamin-D3 and phosphorus supplementation for as long as 48 months was evaluated in six patients with renal hypophosphatemic rickets. Previous phosphorus supplementation of 1,800 to 4,000 mg/sq m of body surface area per day was continued while 1,25-dihydroxyvitamin-D3 at 17 to 80 ng/kg of body weight per day was given orally in place of vitamin-D2. The serum calcium concentration stayed within the normal range in the majority of patients, while the serum phosphorus concentration rose from 2.5 ± 0.4 to 3.4 ± 1.2 mg/100 ml after one month (P < .01). With rare exceptions, serum alkaline phosphatase and parathyroid hormone concentrations stayed normal throughout the study. Healing of rickets was demonstrated by radiography. In five patients, growth velocity was evaluated for 12 months before and after therapy. Growth accelerations were 123% to 235% of that expected for changes in chronologic age and 114% to 200% expected for changes in bone age after therapy. Orally administered, 1,25-dihydroxyvitamin-D3 increased renal calcium excretion and calcium retention was achieved by virtue of the decreased fecal calcium loss. In contrast, 1,25-dihydroxyvitamin-D3, even at doses up to 4 µg/day (80 ng/kg/day) did not significantly alter renal phosphaturia. The phosphorus retention was therefore achieved as the result of the decreased fecal phosphate excretion. The absence of hypercalcemia even at high doses of 1,25-dihydroxyvitamin-D3 and the enhanced linear growth support the long-term therapeutic value of 1,25-dihydroxyvitamin-D3 in renal hypophosphatemic rickets.

Possible link between vitamin D and hyperoxaluria in patients with renal stone disease

1993 ◽  
Vol 84 (1) ◽  
pp. 51-54 ◽  
Author(s):  
Sandro Giannini ◽  
Martino Nobile ◽  
Rocco Castrignano ◽  
Tecla Pati ◽  
Andrea Tasca ◽  
...  
Keyword(s):  
Vitamin D ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Urinary Oxalate ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Stone Formers ◽  
Group 2 ◽  
Urinary Oxalate Excretion ◽  
Group 1

1. Vitamin D seems to play an essential role in the pathogenesis of idiopathic hypercalciuria at least in part via intestinal hyperabsorption of calcium. Hyper-absorption of calcium, in turn, might enhance the intestinal uptake of free oxalate, thus leading to hyperoxaluria. To verify this hypothesis we studied 75 calcium-stone-formers subdivided as follows: group 1 (15 patients) with isolated hyperoxaluria; group 2 (25 patients) with hyperoxaluria and hypercalciuria; group 3 (22 patients) with isolated hypercalciuria; group 4 (12 patients) with no metabolic abnormalities. 2. As expected, urinary calcium excretion differed in the various groups (P < 0.001), being highest in groups 2 and 3; urinary oxalate excretion, by definition highest in groups 1 and 2, was even more pronounced in group 2 than in group 1 (P < 0.05). Although in the normal range, the serum 1,25-dihydroxyvitamin D concentration was higher (P < 0.001) in the two hypercalciuric groups (2 and 3), showing peak levels in group 2. 3. When the data from the 75 stone-formers were pooled, there was a positive correlation between the serum concentration of 1,25-dihydroxyvitamin D and urinary calcium excretion (P < 0.001) and urinary oxalate excretion (P < 0.003), the latter relationship also being present when only the two hypercalciuric groups (groups 2 and 3) were considered together (P < 0.05). 4. Our data seem to confirm a relevant role for the vitamin D system in the pathogenesis of calcium nephrolithiasis due to increased intestinal calcium absorption, but also because this in turn induces a greater intestinal absorption of oxalate, thus leading to the occurrence or exacerbation of hyperoxaluria.

1,25-DIHYDROXYCHOLECALCIFEROL IN HYPOPHOSPHATAEMIC OSTEOMALACIA PRESENTING IN ADULTS

1978 ◽  
Vol 88 (2) ◽  
pp. 408-416 ◽  
Author(s):  
G. Offermann ◽  
G. Delling ◽  
M. R. Haussler
Keyword(s):  
Late Onset ◽  
Bone Mineralization ◽  
Urinary Calcium ◽  
Primary Defect ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Hydroxyproline Excretion ◽  
Dose Dependent ◽  
Hypophosphataemic Osteomalacia

ABSTRACT The effects of exogenous 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in two adults with late-onset hypophosphataemic osteomalacia were studied. In the presence of elevated 25-hydroxyvitamin D levels 1,25(OH)2D3 improved intestinal 17Ca absorption and increased urinary calcium, phosphate and hydroxyproline excretion. Hypophosphataemia, parathyroid hormone and bone mineralization were not significantly affected. The rise of the 1,25-dihydroxyvitamin D concentrations was dose dependent. The results indicate that the impaired renal phosphate conservation - the primary defect in this disorder - is not corrected by exogenous 1,25-dihydroxycholecalciferol.

The Effect of Long-Term Mestranol Administration on Calcium and Phosphorus Homeostasis in Oophorectomized Women

1971 ◽  
Vol 41 (3) ◽  
pp. 233-236 ◽  
Author(s):  
J. M. Aitken ◽  
D. McKay Hart ◽  
D. A. Smith
Keyword(s):  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Hormone Activity ◽  
Phosphorus Excretion ◽  
Calcium And Phosphorus ◽  
Urinary Phosphorus Excretion ◽  
Parathyroid Hormone Activity

1. A group of women who had undergone hysterectomy and bilateral salpingooophorectomy were studied and subsequently given either 20–40 μg of mestranol per day or a placebo for 1 year. 2. The administration of mestranol to these oophorectomized women for 1 year was associated with significant falls in serum calcium and phosphorus concentrations, a fall in urinary calcium excretion and a rise in relative urinary phosphorus excretion. 3. It is suggested that these results are consistent with an increase in sensitivity to calcitonin and that the relative hyperphosphaturia reflects a compensatory rise in parathyroid hormone activity.

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