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Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women

BMJ 1994; 308 doi: (Published 23 April 1994) Cite this as: BMJ 1994;308:1081
  1. M C Chapuy,
  2. M E Arlot,
  3. P D Delmans,
  4. P J Meunier
  1. Institut National de la Sante et de la Recherche Medicale U 234. Service de Rhumatologie et de la Pathologie Osseuse, Pavillon F, Hopital Edouard Herriot, 69437 Lyons Cedex 3, France
  • Accepted 26 August 1993

We recently showed that daily supplementation with 1.2 g calcium and 800 IU cholecalciferol over 18 months substantially decreased the risk of hip fractures and other non-vertebral fractures in elderly women living in nursing homes.1 We report the results of a further 18 months of treatment.

Subjects, methods, and results

A total of 3270 mobile elderly women (mean age 84 (SD 6) years) living in 180 nursing homes were enrolled in the study. Half the women received 1.2 g calcium daily in the form of tricalcium phosphate, together with 800 IU (20 μg) cholecalciferol; the other half received a double placebo. All subjects were followed up every six months; biochemical variables were measured at baseline and every year in a subgroup of 52 women. Hip fractures and all non-vertebral fractures were separately analysed using a log rank test and an actuarial method; 95% confidence intervals are given.

The table shows the effects of supplementation on the number of fractures. The active treatment analysis show that after 36 months of follow up the probability of hip fractures (−29%; P<0.01) and all non- vertebral fractures (−24%; P<0.01) was reduced in the treatment group. The odds ratio for the decreased risk of hip fracture was 0.70 (95% confidence interval 0.62 to 0.78) and for all non-vertebral fractures 0.70 (0.51 to 0.91). The intention to treat analysis shows that 17.2% fewer subjects had one or more non-vertebral fractures (255 v 308, P<0.02) and 23.0% fewer subjects one hip fracture (137 v 178, P<0.02) in the treatment group. In addition, there was a decreased probability of hip fractures (P<0.02) and all non-vertebral fractures (P<0.01), with an odds ratio of 0.73 for hip fractures (0.62 to 0.84) and 0.72 (0.60 to 0.84) for all non-vertebral fractures. Women with a raised mean serum parathyroid hormone concentration and low serum 25 - hydroxycholecalciferol concentration at baseline had normal values after three years of treatment.1 By contrast, in the placebo group parathyroid hormone concentration significantly increased from baseline values and 25-hydroxycholecalciferol concentration remained low. We measured femoral bone density at baseline in 128 women and found a significant negative correlation between density and serum parathyroid hormone concentrations before (r=0.34) and after adjustment for age (r=0.25).

Effects of cholecalciferol and calcium supplementation on numbers of fractures in elderly women

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Our results are similar to those of Khaw et al, who found that bone density at lumbar spine and femoral neck in 138 women aged 45-65 was significantly negatively correlated with serum parathyroid hormone concentration after adjustment for age and body mass index (−0.18 and - 0.21 respectively).2 Our results also confirm a continued preventive effect of calcium and cholecalciferol supplementation on the risk of hip fracture.1

Increased parathyroid hormone secretion in elderly women seems to increase the risk of hip fractures. Hypovitaminosis D and a low calcium intake are the main determinants of this senile secondary hyperparathyroidism,3, 4 but their relative contributions to the risk of fracture are difficult to assess. Vitamin D and calcium reverse and prevent the effects of hyperparathyroidism on bone3 and should be increased in elderly people with a low femoral bone mass and high serum parathyroid hormone concentrations or low serum 25- hydroxycholecalciferol concentrations. The best way would be naturally - by exposure to sunlight and increased consumption of dairy products - but elderly people are notoriously reluctant to change their lifestyle. Therefore daily supplementation with cholecalciferol and calcium salts is the most certain and safest way to reduce the risk of hip fracture because the side effects of physiological doses are negligible. An annual injection of calciferol has also been proposed but did not significantly reduce the number of hip fractures.5 This work was supported by a grant from the Institut National de la Sante et de la Recherche Medicale and Caisse Nationale d'Assurance Maladie des Travailleurs Salaries and a contribution from Ministere de la Recherche et de I'Enseignement Superieur-Aliment 2000. Duphar and Merck-Clevenot Laboratories provided the cholecalciferol (Devaron) and tricalcium phosphate (Ostram) respectively.


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