Calcium-phosphate product

Use in patients who have concomitant hypercalcemia and/or a calcium/phosphate product >55... 

Prolonged exposure to aluminium in patients with chronic renal insufficiency can be involved in the pathogenesis of uremic pruritus, and increased calcium phosphate production seems to be an additional predisposing factor (75) certainly the incidence and intensity of pruritus in these uremic patients have been found to be related to the circulating concentrations of aluminium. 

Two renal transplant recipients developed calcinosis cutis (tender erythematous subcutaneous nodules with induration, ulceration, and necrosis), confirmed by bone scan and biopsies, at the site of subcutaneous administration of nadroparin (72). Both had secondary hyperparathyroidism and a raised calcium-phosphate product at the time of administration. The authors suggested that the high concentration of calcium in nadroparin (220 mmol/1) had been an important factor, since in the same patients subcutaneous injections of nicomorphine or dalteparin did not cause subcutaneous nodules. Three more cases were found after retrospective examination of all 51 adult patients who underwent a renal transplantation in the same hospital during 7 months, and there were no other cases of calcinosis cutis at the injection sites of low molecular weight heparins after nadroparin was replaced by dalteparin. 

Tribasic calcium phosphate occurs naturally as the minerals hydroxylapatite, voelicherite, and whitlockite. Commercially, it is prepared by treating phosphate-containing rock with sulfuric acid. Tribasic calcium phosphate powder is then precipitated by the addition of calcium hydroxide. Tribasic calcium phosphate is alternatively prepared by treating calcium hydroxide from limestone with purified phosphoric acid. It may also be obtained from calcined animal bones.Some tribasic calcium phosphate products may be prepared in coarser, directly compressible forms by granulating the powder using roller compaction or spray drying. 

It appears that increased plasma phosphate concentrations are not directly toxic (Sutters et al 1996). Hypocalcemia and metastatic soft-tissue calcification caused by hyperphosphatemia result from the calcium/phosphate product exceeding that required for precipitation of calcium phosphate in the tissues (Macintire 1997, Sutters et al 1996). 

The elevated calcium-phosphate product results in precipitation in arteries, joints, soft tissues, and the viscera. This can result in tissue ischemia, termed calciphylaxis. 

Parenteral phosphorus supplementation is associated with risks of hyperphosphatemia, metastatic soft tissue deposition of calcium-phosphate product, hypomagnesemia, hypocalcemia, and hyperkalemia or hypernatremia (caused by intravenous phosphorus salt) (Table 49-9). Inappropriate administration of large doses of parenteral phosphorus over relatively short time periods has resulted in symptomatic hypocalcemia and soft-tissue calcification. The rate of infusion and choice of initial dosage should therefore be based on severity of hypophosphatemia, presence of symptoms, and coexistent medical conditions. Patients should be closely monitored with frequent (every 6 hours) serum phosphorus determinations for 48 to 72 hours after starting intravenous therapy. It may be necessary to continue administration of intravenous phosphorus for several days in some patients, while other patients may be able to tolerate an... 

The relationship of the inorganic phosphate concentration to bone mineral is more complex. The normal range of plasma phosphate concentration is much larger than that of calcium, presumably because the phosphate concentration (unlike that of calcium) is influenced by dietary intake of phosphorus and by urinary excretion and because the parathyroids intervene to correct major changes in calcium concentration. The skeleton thus controls plasma calcium at a constant level but permits relatively large variations in plasma phosphate there is therefore no constant [calcium] [phosphate] product in plasma or tissue fluid... 

B4. Basset, C. A. L., and Nordin, B. E. C., The calcium-phosphate product in an in vitro system of surviving bone. Acta Orthopaed. Scand. 28, 241-254 (1959). 

Table 3L2. Typical trace element limits in slaked lime for calcium phosphate production...

Table 7. Variable parameters of some calcium phosphate synthesis and calcium phosphate products phase composition after thermal treatment at 1100 C for 1 h...

Calciphylaxis is a rare life-threatening disorder characterized hy progressive vascular calcification and ischemic tissue loss in patients with end-stage renal disease (Wood et al. 1997 Hafner et al. 1998 Karpman et al. 2003 Guvel et al. 2004). The pathogenesis is poorly understood it is likely the result of a multiplicity of co-morbid factors or events. Disorders that are most often implicated include chronic renal failure, hypercalcemia, hyperphosphatemia, an elevated calcium-phosphate product and secondary hyperparathyroidism. Very rare cases of calciphylaxis not associated with chronic renal failure have been reported with breast cancer, hyperparathyroidism and alcoholic cirrhosis. 

Sampathkumar et al. 2006 Single treatment of 34 extended release nicotinic acid (375 mg) tablet in patients on haemodialysis for a mean period of eight months. This was associated with a significant decrease in both plasma phosphate and calcium phosphate product. Restrepo et al. 2008 In nine patients with CKD and on dialysis treated with 1000 mg nictonic acid for eight months decreased LDL-c, triglyceride and increased HDL-c. The authors recommended that nicotinic acid is efficient, very well tolerated and economical in comparison with other drugs, which makes it ideal for the treatment of patients with hyperlipidaemia and refractory hyperphosphatemia to classical treatments. 

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