Fractures

45% of 1155 respondents indicated that the impact of HRT on increasing or decreasing the risk of fractures was very certain.

58% of 1153 respondents indicated that regarding fractures, HRT was likely to be very beneficial.

There was a significant positive correlation between respondent’s level of certainty and their estimate of benefit. (Spearman’s rho = 0.56[1] p<0.0001) Those who felt more certain were more likely to believe that HRT had a beneficial effect on fracture rates.

The impact of HRT on fracture rates is probably known and may be mildly beneficial.

All of the evidence from RCTs is consistent with the belief that long term HRT reduces fracture risk but the benefit may be small. One RCT has suggested that in women with established osteoporosis, HRT may reduce the rate of lower vertebral fractures.[2] However, hip fractures are more important for patients. We are not aware of any direct evidence from RCTs of a reduction in hip fractures from HRT even in women with osteoporosis. Reports of two trials of HRT for women without osteoporosis claim lower rates of non-vertebral fractures of borderline statistical significance. However the first of these trials used questionable statistical “adjustments”.[3] The second trial found significantly less forearm fractures in the HRT group but there was no significant difference in the total number of fractures.[4] Most of the participants in this trial were not randomised and there was no placebo so the results are not reliable.

HRT does reduce loss of bone density.[5] However, contrary to popular belief, bone density is not good for predicting who is or is not at high risk of fractures as shown in the graph below.[6] We should also remember that fractures result from many causes and bone density is just one factor along with balance, environment, sedating medications, etc.

Bone density is not a good test for distinguishing between high and low fracture risk because there is so much overlap between the curves for women who will have hip fractures versus those who will not.[6]

If Ann does not have osteoporosis then the best quality evidence relevant for Ann is the HERS trial.[7] The HERS trial found no significant difference in the rate of fractures. 10% of women in the placebo group had fractures vs 9.4% in the HRT group. (p = 0.7 ie the probability of the 0.6% difference arising from chance alone is 70%).

[1] Spearman’s rho: 0 = no correlation, 1 = 100% “straight line” correlation

[2] Lufkin EG et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 1992 Jul 1;117(1):1-9

[3] Komulainen MH et al. HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial. Maturitas 1998 Nov 30;31(1):45-54

[4] Mosekilde L et al. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish osteoporosis prevention study. Maturitas 2000 Oct 31;36(3):181-93

[5] Lindsay R, Hart DM, Forrest C, Baird C. Prevention of spinal osteoporosis in oophorectomised women. Lancet. 1980;ii:1151-1153.

[6] Green CJ et al. Bone Mineral Density Testing: does the evidence support its selective use in well women. BCOHTA 97:2T, Vancouver, Dec 1997 www.chspr.ubc.ca

[7] Hulley et al. Randomized trial of estrogen plus progestogen for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998;280:7:605-13