The impact of dietary calcium intake and vitamin D status on the effects of zoledronate.
We investigated whether baseline dietary calcium intake or vitamin D status modified the effects of zoledronate. Neither variable influenced the effect of zoledronate on bone mineral density, bone turnover, or risk of acute phase reaction, suggesting that co-administration of calcium and vitamin D supplements with zoledronate may not always be necessary.


BACKGROUND
Calcium and vitamin D supplements are often co-administered with bisphosphonates, but it is unclear whether they are necessary for therapeutic efficacy or minimizing side effects of bisphosphonates. We investigated whether baseline dietary calcium intake or vitamin D status modified the effect of zoledronate on bone mineral density (BMD) or bone turnover at 1 year, or the risk of acute phase reactions (APR).


METHODS
Data were pooled from two trials of zoledronate in postmenopausal women without vitamin D deficiency in which calcium and vitamin D were not routinely administered. The cohort (zoledronate n = 154, placebo n = 68) was divided into subgroups by baseline dietary calcium intake (<800 vs. ≥800 mg/day) and vitamin D status [25-hydroxyvitamin D (25OHD) <50 vs. ≥50 nmol/L, and <75 nmol/L vs. ≥75 nmol/L] and treatment × subgroup interactions tested.


RESULTS
There were 52, 86, and 36 % of the zoledronate group and 64, 94, and 46 % of the placebo group that had dietary calcium intake ≥800 mg/day, 25OHD ≥50 nmol/L, and 25OHD ≥75 nmol/L, respectively. There were no significant interactions between treatment and either baseline dietary calcium or baseline vitamin D status for lumbar spine BMD, total hip BMD, the bone turnover markers P1NP and β-CTx, or the risk of an APR. There was also no three-way interaction between baseline dietary calcium intake, baseline vitamin D status, and treatment for any of these variables.


CONCLUSIONS
Baseline dietary calcium intake and vitamin D status did not alter the effects of zoledronate, suggesting that co-administration of calcium and vitamin D with zoledronate may not be necessary for individuals not at risk of marked vitamin D deficiency.
Department of Rheumatology, Auckland City Hospital, Auckland, New Zealand.
S
S
Bourke
M J
MJ
Bolland
A
A
Grey
A M
AM
Horne
D J
DJ
Wattie
S
S
Wong
G D
GD
Gamble
I R
IR
Reid
D000210:Acute-Phase Reaction / Q000139:chemically induced; D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018565:Food-Drug Interactions / Q000502:physiology*; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D002136:Calcium, Dietary; D004164:Diphosphonates; D007093:Imidazoles; D014807:Vitamin D; D000077211:Zoledronic Acid; C104450:25-hydroxyvitamin D