Osteoporosis is a well-defined health risk in cystic fibrosis (CF) patients due to many factors. Vitamin D insufficiency, despite routine cholecalciferol supplementation in CF patients, may contribute to a relative secondary hyperparathyroidism and possibly deficient bone mineralization. An alternate form of vitamin D, calcitriol, was studied to determine short-term effects on fractional calcium absorption and other calciotropic markers in 10 adult CF subjects and in 10 age-, sex- and body mass index (BMI)-matched controls. Serum fractional absorption of Ca-45 was determined after a calcium-containing meal prior to calcitriol intervention. Other measurements included serum parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and urinary calcium:creatinine and N-telopeptide (NTx) concentrations. Both groups were then given calcitriol (0.5 mug p.o. b.i.d. for 14 days) and restudied following the same protocol. Both groups increased their fractional absorption of Ca-45 after calcitriol (p=0.015 CF subjects, p=0.001 controls), although calcitriol tended to be less effective in the CF group compared with the controls (p=0.055). Post-prandial serum PTH concentrations were suppressed compared with baseline in both groups (p=0.03 CF subjects, p=0.006 controls). Urinary NTx concentrations, a marker for bone resorption, decreased significantly in CF subjects after calcitriol (96.0+/-16.0 vs 63.9+/-12.7 nmol BCE/mmol Cr, p=0.01) and remained unchanged in the control group. The controls had an increase in serum 1,25(OH)(2)D concentrations (69.9+/-4.2 vs 90.7+/-9.6 pmol/l, p=0.02) while there was no significant change in the CF group. Oral calcitriol administration appears to improve markers of calcium balance in adults with CF by increasing fractional absorption of Ca-45 and lowering PTH concentrations, similar to its known effects in healthy subjects, while also suppressing urinary NTx, a marker of bone turnover.