Heterogeneity in Serum 25‐Hydroxy‐Vitamin D Response to Cholecalciferol in Elderly Women with Secondary Hyperparathyroidism and Vitamin D Deficiency

OBJECTIVES: To compare the effects on parathyroid hormone (PTH) and 25‐hydroxy‐vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol. DESIGN: Randomized‐controlled trial with 6‐month follow‐up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Sixty community‐dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism. INTERVENTION: Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D₃ group) or cholecalciferol 1,000 IU/day (daily D₃ group). MEASUREMENTS: Serum PTH, 25(OH)D, calcium, bone‐specific alkaline phosphatase, β‐C‐terminal telopeptide of type I collagen, phosphate, 24‐hour urinary calcium excretion. RESULTS: The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)D<20 ng/mL)], and 36 subjects (60%) had severe deficiency (<10 ng/mL), with no difference between the groups (severe deficiency: intermittent D₃ group, n=18; daily D₃ group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase±standard deviation of 25(OH)D at 6 months was higher in the intermittent D₃ group (22.7±11.8 ng/mL) than in the daily D₃ group (13.7±6.7 ng/mL, P<.001), with a higher proportion of participants in the intermittent D₃ group reaching desirable serum concentration of 25(OH)D ≥ 30 ng/mL (55% in the intermittent D₃ group vs 20% in the daily D₃ group, P<.001). Mean percentage decrease of PTH in the two groups was comparable, and at 6 months, a similar proportion of participants reached normal PTH values. 25(OH)D response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values. CONCLUSION: Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher‐dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet‐higher doses will be required for adequate vitamin D repletion.