Calcium and Vitamin D Supplementation is an Ineffective Strategy for the Prevention of Fractures in Older People

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1 Calcium and Vitamin D Supplementation is an Ineffective Strategy for the Prevention of Fractures in Older People For the Motion: Professor Roger Francis, Institute for Ageing and Health, Newcastle University, UK.

2 CONFLICTS OF INTEREST Advisory Board: Servier Speaker: Shire Eli Lilly Servier Amgen/GSK

3 RATIONALE FOR CALCIUM AND VITAMIN D SUPPLEMENTATION Ensure that calcium intake is sufficient to offset losses in the urine, digestive juices and sweat. Correct any underlying vitamin D deficiency. As an adjunct to other osteoporosis treatments. Decrease PTH, reduce bone loss and improve muscle function. Prevent falls and fractures!

4 DIETARY CALCIUM REQUIREMENTS: UK Dietary reference values for calcium in UK based on factorial calculation, taking into account absorption and obligatory losses. Estimated Average Requirement (EAR) for adults 550 mg/day. Lower Reference Nutrient Intake (EAR 2 SDs) 400 mg/day. Upper Reference Nutrient Intake (EAR + 2 SDs) 700 mg/day. Department of Health, HMSO, 1991

5 CALCIUM INTAKE IN THE UK Mean Intake in Women Age 65-74: 704 mg/day Age 75-84: 680 mg/day Age > 85: 647 mg/day Prevalence in Women (%) Intake < LRNI (400 mg/day) > 85 Age (years) Finch et al, National Diet and Nutrition Survey. London: The Stationary Office 1998

6 PREVALENCE OF VITAMIN D DEFICIENCY IN THE UK Prevalence (%) Serum 25OHD < 25 nmol/l In Care 85 + In Care Finch et al, National Diet and Nutrition Survey. London: The Stationary Office 1998 Men Women

7 CALCIUM AND VITAMIN D SUPPLEMENTATION RCT in 3,270 women (mean age 84 years). All lived in nursing homes or apartment blocks for the elderly. Randomised to receive 1.2 g calcium and 800 IU vitamin D 3 daily or placebo. Chapuy et al, N Engl J Med 1992; 327: Hip Fractures (%) Placebo 43% Calcium & Vitamin D

8 RCT in 5,292 communitydwelling older women or men with a low trauma fracture. Randomised to vitamin D, calcium, vitamin D & calcium or double placebo. Main outcome was further low trauma fractures. RECORD STUDY RECORD Trial Group, Lancet 2005; 365: No reduction in falls or fractures

9 RECORD STUDY RECORD Trial Group, Lancet 2005; 365:

10 RECORD STUDY Fracture Risk Hazard Ratio ITT Analysis HR 0.94 CI Per Protocol Analysis HR 0.87 CI RECORD Trial Group, Lancet 2005; 365: Grant et al, Lancet 2005; 366:

11 NORTHERN & YORKSHIRE STUDY No reduction in falls, fractures or mortality Porthouse et al, Br Med J 2005; 330: Questionnaires sent to older women on GP Age/Sex Registers. Recruited 3,315 women aged > 70 with risk factor for hip fracture. Eligible subjects randomised to control group or to nurseled clinic. Calcium and vitamin D started if no contraindication.

12 WOMEN S HEALTH INITIATIVE STUDY Trial in 36,282 postmenopausal women aged years, randomised to calcium (1,000 mg) and vitamin D (400 IU) or placebo daily. Small improvement in BMD with calcium & vitamin D, but no overall reduction in fracture risk. Reduction in hip fracture risk in subjects persisting with study medication (HR 0.71; 95% CI 0.52 to 0.97). Jackson et al, N Engl J Med 2006; 354:

13 THE PROBLEM OF COMPLIANCE! A world-wide problem of striking magnitude WHO, 2003

14 SUPPLEMENTATION AND FRACTURES Tang et al, Lancet 2007; 370:

15 SUPPLEMENTATION AND FRACTURES Vitamin D Calcium and Vitamin D Boonen et al, J Clin Endocrinol Metab 2007; 92:

16 SAFETY OF SUPPLEMENTATION Primum non nocere

17 SAFETY OF SUPPLEMENTATION Good safety record in RCTs Hypercalcaemia Hypercalciuria Renal insufficiency Renal stones Vascular and soft tissue calcification Cardiovascular disease

18 WOMEN S HEALTH INITIATIVE STUDY 744 deaths in supplemented group and 807 in the placebo group (HR 0.91; 95% CI 0.83 to 1.01). No significant difference in cardiovascular disease or cancer. Renal stones reported in 449 women (2.47%) in the supplemented group compared with 381 (2.10%) in the placebo group (HR 1.17; 95% CI 1.02 to 1.34). Jackson et al, N Engl J Med 2006; 354:

19 CALCIUM SUPPLEMENTATION AND CARDIOVASCULAR DISEASE Secondary analysis of an RCT of calcium supplementation on BMD and fracture incidence showed an increase in MI (Reid et al, 2008). Subsequent meta-analysis of large trials of calcium supplementation: Five studies with patient level data (8,151 participants, median follow-up 3.6 years) and eleven studies with trial level data (11,921 participants, mean duration 4.0 years). Bolland et al, Br Med J 2010; 341: c3691.

20 CALCIUM SUPPLEMENTATION AND CARDIOVASCULAR DISEASE Bolland et al, Br Med J 2010; 341: c3691.

21 CALCIUM & VITAMIN D AND CARDIOVASCULAR DISEASE Bolland et al, Br Med J 2011; 342: d2040.

22 CALCIUM & VITAMIN D AND CARDIOVASCULAR DISEASE In women not taking calcium supplements at randomisation, hazard ratios for cardiovascular events with calcium and vitamin D ranged from 1.13 to 1.22 (significance p = 0.04 to 0.05). In women taking calcium at baseline, cardiovascular risk did not alter with allocation to calcium and vitamin D. Bolland et al, Br Med J 2011; 342: d2040.

23 CALCIUM & VITAMIN D AND CARDIOVASCULAR DISEASE Bolland et al, Br Med J 2011; 342: d2040.

24 CALCIUM & VITAMIN D AND CARDIOVASCULAR DISEASE Abrahamsen & Sahota, Br Med J 2011; 342: d2080.

25 CALCIUM AND VITAMIN D SUPPLEMENTATION French RCT suggests that it decreases fracture risk in institutionalised older people. Little evidence that it is effective in fracture prevention in community dwelling older people, as long term compliance is poor. Calcium supplementation poorly tolerated. Concern about potential effect on renal stones and cardiovascular disease.

26 EFFICACY v EFFECTIVENESS Efficacy: Measures how well treatment works in clinical trials or laboratory studies. Effectiveness : How well a treatment works in clinical practice.

27 EFFECTIVENESS OF SUPPLEMENTATION Supplementation is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance Prince et al, Arch Intern Med 2006; 166:

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