The Efficacy of Vitamin D2and Oral Phosphorus Therapy in X-Linked Hypophosphatemic Rickets and Osteomalacia *

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Abstract
Conventional treatment of X-linked hypophosphatemic rickets/osteomalacia (XLH) is oral phosphorus supplementation in combination with vitamin D2. Although this drug regimen allegedly offers the best therapeutic results for this disorder, the data supporting the efficacy of therapy on bone healing in this disease are incomplete. Thus, in the present study, we investigated the effects of long term phosphorus and vitamin D2 treatment on the characteristic bone disease of XLH. In addition, we correlated effects on the bone abnormalities with therapy-induced changes in calcium and phosphorus homeostasis and vitamin D metabolism. Four untreated subjects with XLH served as age (14–25 yr)- and growth rate-matched controls. They had normocalcemia (9.06 ± 0.12 mg/dl), hypophosphatemia (2.12 ± 0.02 mg/dl), a decreased renal tubular maximum for the reabsorption of phosphate per liter glomerular filtrate (1.95 ± 0.07 mg/dl), negative phosphate balance (−41 ± 12 mg/day), and bone biopsies which showed changes characteristic of osteomalacia. In addition, serum 25-hydroxyvitamin D was 34.5 ± 4.2 ng/ml, and serum 1,25-dihydroxyvitamin D was 30.3 ± 2.8 pg/ml. The effects of long term therapy (18–36 months) with oral phosphorus (2 g/day) and vitamin D2 (50,000–75,000 u/day) were examined in three subjects, aged 13–19 yr. In comparison to controls, treated subjects had a similar serum calcium level (9.06 ± 10 mg/dl) and renal tubular maximum for the reabsorption of phosphate per liter glomerular filtrate (1.97 ± 0.19 mg/dl). In contrast, serum phosphorus (2.93 ± 0.25 mg/ dl) and phosphorus balance (+667 ± 90 mg/day) were significantly increased. In addition, serum 25-hydroxyvitamin D (153.0 ± 4.5 ng/ml) attained supraphysiological levels, which resulted in a significant suppression of the serum 1,25-dihydroxyvitamin D concentration (19.0 ± 2.6 pg/ml). Most importantly, despite therapy, the osteomalacic bone lesion remained equally severe as that in controls. Although mineralization front activity normalized upon treatment, no evidence of decreased unmineralized osteoid was present in biopsies from treated subjects. These data indicate that treatment of XLH with phosphorus and vitamin D2, although improving phosphorus (and calcium) homeostasis, does not completely heal the bone lesions. The advantage of this drug regimen, therefore, remains to be determined.