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Osteoporosis, Teriparatide, and Dosing of Calcium and Vitamin D
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     To the Editor: Teriparatide represents a new class of therapeutic options for osteoporosis. Since it is a parathyroid hormone derivative, many practitioners are concerned about hypercalcemia, which is seen in hyperparathyroidism, and about how best to monitor their patients receiving this therapy. A major study of this compound in the Journal1 stated that transient and chronic hypercalcemia were rare, that changes in vitamin D metabolism occurred, and that manipulation of mineral or drug doses helped lower serum calcium levels. Published data are not available, to my knowledge, however.

    In my initial use of this drug, persistent hypercalcemia (i.e., serum calcium levels of 11 to 11.5 mg per deciliter) developed in three patients. This finding prompted closer surveillance of a subsequent group of 12 treated patients. All 12 patients took extra elemental calcium (mean [±SD] daily dose, 1100 mg), and 10 of them took vitamin D (mean daily dose, 355±200 IU). At baseline and after receiving treatment (i.e., one to three months into therapy), serum levels of calcium, intact parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were checked more than six hours after injection of the teriparatide, since most patients administered the drug at bedtime. Levels of intact parathyroid hormone decreased and those of 25-hydroxyvitamin D showed a downward trend (Table 1). Levels of 1,25-dihydroxyvitamin D and total serum calcium increased. In two thirds of the measurements, the values for 1,25-dihydroxyvitamin D levels exceeded the 95 percent confidence limit (mean, 98.9±26.4 pg per milliliter); in the remaining levels, the values were below the confidence limit (36.5±6.6 pg per milliliter). The change in serum calcium levels tended to correlate positively with 1,25-dihydroxyvitamin D levels (Spearman's r=0.65; one-tailed P value, 0.08) and inversely with 25-hydroxyvitamin D (Spearman's r=–0.66; one-tailed P value, 0.054). The substantial rise in serum 1,25-dihydroxyvitamin D levels in the presence of decreased levels of intact parathyroid hormone and increased levels of calcium suggested that teriparatide affected the serum concentration of the vitamin even in the presence of physiological signals that normally decrease its concentration.

    Table 1. Levels of Serum Calcium, Intact Parathyroid Hormone (PTH), 25-Hydroxyvitamin D (25(OH)D), and 1,25-Dihydroxyvitamin D (1,25(OH)2D) before and after Treatment with Teriparatide.

    From the clinical perspective, the guidelines of the National Osteoporosis Foundation and other medical-specialty guidelines for calcium and vitamin D use may suggest doses that are too high for some patients taking this drug. When teriparatide therapy is begun for my patients, daily elemental calcium is maintained at 1000 mg or less, to keep the level of serum calcium below 10 mg per deciliter. Supplemental vitamin D is not given if the basal level is greater than 20 ng per milliliter. In the absence of directives for the use of vitamins and minerals in the treatment of patients taking teriparatide, this approach may be useful for practitioners as a way to prevent hypercalcemia in clinical practice.

    Angelo A. Licata, M.D., Ph.D.

    Cleveland Clinic Foundation

    Cleveland, OH 44195

    Dr. Licata reports having received lecture fees from Eli Lilly and having served as a clinical investigator for Eli Lilly and NPS Pharmaceuticals.