Hypophosphatemic osteomalacia

Chines A, Pacifici R. 1990. Antacid and sucralfate-induced hypophosphatemic osteomalacia A case report and review of the literature. Calcif Tissue Int 47 291-295. 

Tumor-induced osteomalacia (oncogenic hypophosphatemic osteomalacia) is also characterized by excessive urinary excretion of phosphate, and hence hypophosphatemia and low circulating calcitriol. Removal of the tumor results in normalization of phosphate excretion and... 

Hypercalcemia persists for many months after the cessation of excessive intakes of vitamin D, because of the accumulation of the vitamin in adipose tissue and its slow release into the circulation. The introduction of calcitriol and 1 a -hydroxycalcidiol for the treatment of such conditions as hypoparathyroidism, renal osteodystrophy, hypophosphatemic osteomalacia, and vitamin D-dependent rickets has meant that hypercalcemia is less of a problem than when high doses of vitamin D were used in the treatment of these conditions. Because calcitriol has a short half-life in the circulation, the resultant hypercalcemia is of shorter duration than after cholecalciferol, and adjustment of the dose is easier. 

Osteomalacia and rickets may also occur because of phosphate depletion. The most common cause of rickets in the United States is hypophosphatemic osteomalacia (also known as hypophosphatemic vitamin D-resistant rickets and vitamin D-resistant rickets).This disorder is an X-linked dominant inherited trait characterized by renal phosphate wasting. Tubular phosphate wasting can also occur sporadically in adults and as part of Fanconi syndrome. Certain rare mesenchymal tumors may also produce a phosphaturic factor (phosphatonin or FGF-23), resultmg in renal phosphate wasting and osteomalacia. 

Osteomalacia may be produced by phosphate depletion (L19), which may occur as the result of intravenous hyperalimentation (L12) or the prolonged consumption of aluminum hydroxide-containing antacids (B26, DIO). Patients with hypophosphatemic osteomalacia may have normal serum alkaline phosphatase values (B26, DIO). (See also Section 6.4.)... 

The combination of hypophosphatemia, vitamin D resistance, osteomalacia, and rickets is seen in a number of syndromes (W24). These include (a) familial hypophosphatemic vitamin D-resistant rickets, a sex-linked, dominant disorder (P3), (b) familial vitamin D dependency, an autosomal recessive disorder due to la-hydroxylase deficiency (F19), and (c) nonfamilial hypophosphatemic osteomalacia (D9), considered by some workers (P3) to be a separate disease entity because of its late onset, its severity, and its lack of response to therapy. In addition, there are many inherited and acquired disorders which are associated with impairment of renal tubular reabsorption of phosphate, and these may be accompanied by hypophosphatemia, rickets, and relative vitamin D resistance. Serum alkaline phosphatase values in these disorders correlate poorly with the severity of the disease (A14) and with the response to therapy (E4, MclO, P7, S50). 

Skeletal disease is common in patients with renal failure treated by chronic dialysis. The majority of these patients have histologically demonstrable bone disease, even in the absence of clinical symptoms (B21). However, serum alkaline phosphatase activities are either within reference limits or only moderately elevated (B21), with spectacular elevations occurring only rarely in both adults (B21, KIO) and children (P34). High serum alkaline phosphatase values have been described in patients on chronic dialysis with severe hypophosphatemic osteomalacia (M3). 

Urinary tract Hypophosphatemic osteomalacia due to Fanconi s syndrome occurred in a 40-year-old man there were hyperphospha-turia, hypercalciuria, glycosuria, and massive aminoaciduria [30 ]. In another case, a 66-year-old man who had been taking adefovir for more than 4 years developed osteomalacia with hypophosphatemia [31 ]. 

Musculoskeletal Severe hypophosphatemic osteomalacia occurred in a 42-year-old man with hepatitis B virus-related chronic liver disease after he had taken adefovir dipivoxil 10 mg/day for 6 months the bone lesions resolved when the hypophosphatemia was corrected... 

Kim du H, Sung DH, Min YK. Hypophosphatemic osteomalacia induced by low-dose adefovir therapy focus on manifestations in the skeletal system and literature review. J Bone Min Metab 2013 31(2) 240-6. 

Wu C, Zhang H, Qian Y, Wang L, Gu X, Dai Z. Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil a case report and literature review suggesting ethnic predisposition. J Clin Pharm Ther 2013 38(4) 321-6. 

Renal elimination of phosphorus is regulated by PTH, calcitriol, growth hormone, insulin, and insulin-like growth factors. While the above-mentioned hormones show a number of other effects, the existence of a hormone affecting selectively the extracellular concentration of phosphorus is expected. The task of this hormone with phosphaturic effect has been speculated about from the beginning of the 1990s. It was named phosphatonin, and its increased concentration is found especially in patients with osteomalacia (tumor-induced osteomalacia, X-linked hypophosphatemic rickets, epidermal nevus). The phosphaturic effect of... 

Harrell RM, Lyles KW, Harrelson JM, Friedman NE, Drezner MK. Heahng of bone disease in X-linked hypophosphatemic rickets/osteomalacia. J CUn Invest 1985 75 1858-68. 

P3. Parfitt, A. M., Hypophosphatemic vitamin D refractory rickets and osteomalacia. Orthop. Clin. N. Amer. 3, 653-680 (1972). 

Conditions associated with abnormalities in calcitriol synthesis or response can cause rickets in children and osteomalacia in adults. Specific disorders include X-linked hypophosphatemic rickets due to mutations in the PHEX endoprotease, Vitamin D-dependent rickets due to mutations in la-hydroxylase, and hereditary l,25-(OH)J) resistance due to mutations in the VDR. 

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