Clinical and laboratory safety of one year's use of a combination calcium + vitamin D tablet in ambulatory elderly women with vitamin D insufficiency: results of a multicenter, randomized, double-blind, placebo-controlled study.
OBJECTIVE
This article presents the results of an evaluation of the clinical and laboratory safety of a 1-year course of treatment with a combination calcium and vitamin D tablet in ambulatory women aged >65 years with vitamin D insufficiency.


METHODS
In a multicenter, randomized, double-blind, placebo-controlled study conducted in France, women with a 25-hydroxyvitamin D level < or =12 ng/mL were randomized to receive either a combination tablet containing calcium carbonate 500 mg and vitamin D3 400 IU taken twice daily or a matching placebo tablet for 1 year. A complete clinical examination was performed at baseline and at 3, 6, 9, and 12 months of treatment; blood and urine samples were collected for laboratory analyses at the same time points. Safety was monitored based on adverse events recorded during the treatment period and on the results of laboratory tests, including measurement of creatinine and uric acid levels.


RESULTS
The study included 192 women (mean [SD] age, 74.6 [6.9] years; mean weight, 64.0 [12.5] kg), 95 in the calcium + vitamin D group and 97 in the placebo group. Fifty women (21/95 [22.1%] calcium + vitamin D, 29/96 [30.2%] placebo) were prematurely withdrawn from the study for various reasons, with no difference in withdrawals between groups. Treatment-related adverse events were reported in 21 (22.1%) and 23 (24.0%) women in the respective treatment groups. These events consisted mainly of metabolic disorders (9 [9.5%] and 10 [10.4%], respectively), particularly hypercalcemia (6 [6.3%] and 8 [8.3%]) and gastrointestinal disorders (9 [9.5%] and 8 [8.3%]). No major complications directly related to calcium and vitamin D supplementation occurred during the course of treatment. Although renal function was not altered, the group who received calcium + vitamin D had significantly elevated concentrations of serum uric acid compared with those who received placebo (52.3% vs 37.2%; P = 0.046) but not urinary uric acid.


CONCLUSIONS
In these ambulatory elderly women with vitamin D deficiency, supplementation with calcium + vitamin D appeared to be well tolerated over 1 year of treatment. No significant effects on creatinine clearance were observed. However, the proportion of women with elevated serum uric acid concentrations was significantly greater in those who received calcium + vitamin D compared with those who received placebo.
Brazier
Michel
M
Department of Rheumatology, Hôpital Nord, Amiens, France.
Grados
Franck
F
Kamel
Saïd
S
Mathieu
Marc
M
Morel
Alain
A
Maamer
Mohamed
M
Sebert
Jean-Luc
JL
Fardellone
Patrice
P
D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002118:Calcium / Q000652:urine; D002119:Calcium Carbonate / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000627:therapeutic use*; D003401:Creatine / Q000652:urine; D019587:Dietary Supplements; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D010281:Parathyroid Hormone / Q000097:blood; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood; D014808:Vitamin D Deficiency / Q000188:drug therapy*
D050071:Bone Density Conservation Agents; D004338:Drug Combinations; D010281:Parathyroid Hormone; D002762:Cholecalciferol; D014527:Uric Acid; D002119:Calcium Carbonate; D003401:Creatine; D002118:Calcium