JOURNAL OF BONE AND MINERAL RESEARCH Volume 7, Number 6, 1992 Mary Ann Licbert, lnc., Publishers
Letter to the Editor Estrogen Therapy and Variable-Resistance Weight Training To the Editor: The recent study by Notelovitz et al. in the Journal (6583, 1991) does not include a untreated control group or a group given weight training alone. These omissions have two effects. First, the investigators cannot conclude that the estrogen therapy was responsible for this “maintenance” of bone density in the estrogen-treated non-weighttraining group unless there is an untreated control group shown to be losing bone. Indeed. the wide range in annual rates of change in bone density (mean f standard deviation, SD,1.5 f 12.470, confidence internal -6.9 to 9.8%) suggests that about half the 11 non-weight-training subjects taking estrogen were losing bone and about half were gaining bone. Second, the study design does not permit testing whether estrogen and weight training “have a synergistic effect and increase the bone mineral over and above the maintenance characteristic of estrogen replacement therapy alone” as there was no control group receiving weight training alone. The increase in bone density in the estrogen plus weight-training group may have been due to the weight training alone. Thus, it is not possible to conclude that variable-resistance weight training “enhances” the “known” bone-conserving effect of estrogen. The study design needed to address the important issues raised in the paper must include the following groups: placebo controls, estrogen alone, weight training alone, and an estrogen + weight training group. The standard de-
viation of the response to each treatment is unknown. In the study by Notelovitz et al. (1991), the change in spinal bone density after 1 year was about 8 f 5% (mean f SD) in the estrogen plus weight-training group. Table 1 illustrates the sample sizes needed to demonstrate a desired synergistic or additive effect assuming three different SD of 4, 7, or 9% in the response for 80% power at the p = 0.05 level of significance. The effect of weight training alone is not known. However, estrogen + weight training is unlikely to increase bone density more than about 5 % over and above the effect of the weight training alone because estrogens usually maintain bone density, or increase it by only 1-3% over a 1-2 year period. If this is correct, then a minimum of 21 subjects per group will be needed to demonstrate this effect. The numbers will be larger if dropouts are factored into the estimate and/or the standard deviation of the response to either treatment is greater. This might be expected with studies of longer duration and occurred in the study by Notelovitz et al. where 13 subjects dropped out and the SD was 12% in the estrogen-alone group. A smaller effect will be more difficult to demonstrate and will be biologically less meaningful; a larger effect is possible, of course, but seems unlikely. Thus, this study is very difficult to conduct given the difficulties in compliance and the probable small size of any additive effect of weight training plus estrogen.
TABLE1. DESIRED DIFFERENCE (070) BETWEEN WEIGHTTRAINING VERSUSWEIGHTTRAININGPLUSESTROGEN
Assumed standard deviation in response (Yo)
5 7 9
Sample size per group
I
2
3
4
5
6
7
525 1029 1701
131 257 576
58 114 234
33 64 132
21 41 84
IS 29 58
11 21 43
Dr. Ego Seeman Department of Endocrinology Austin Hospital Heidelberg, Melbourne, Australia
709
8
8 16 33
9
1
6 13 26
0
5 10 21
Letter to the Editor Estrogen Therapy and Variable-Resistance Weight Training To the Editor: The recent study by Notelovitz et al. in the Journal (6583, 1991) does not include a untreated control group or a group given weight training alone. These omissions have two effects. First, the investigators cannot conclude that the estrogen therapy was responsible for this “maintenance” of bone density in the estrogen-treated non-weighttraining group unless there is an untreated control group shown to be losing bone. Indeed. the wide range in annual rates of change in bone density (mean f standard deviation, SD,1.5 f 12.470, confidence internal -6.9 to 9.8%) suggests that about half the 11 non-weight-training subjects taking estrogen were losing bone and about half were gaining bone. Second, the study design does not permit testing whether estrogen and weight training “have a synergistic effect and increase the bone mineral over and above the maintenance characteristic of estrogen replacement therapy alone” as there was no control group receiving weight training alone. The increase in bone density in the estrogen plus weight-training group may have been due to the weight training alone. Thus, it is not possible to conclude that variable-resistance weight training “enhances” the “known” bone-conserving effect of estrogen. The study design needed to address the important issues raised in the paper must include the following groups: placebo controls, estrogen alone, weight training alone, and an estrogen + weight training group. The standard de-
viation of the response to each treatment is unknown. In the study by Notelovitz et al. (1991), the change in spinal bone density after 1 year was about 8 f 5% (mean f SD) in the estrogen plus weight-training group. Table 1 illustrates the sample sizes needed to demonstrate a desired synergistic or additive effect assuming three different SD of 4, 7, or 9% in the response for 80% power at the p = 0.05 level of significance. The effect of weight training alone is not known. However, estrogen + weight training is unlikely to increase bone density more than about 5 % over and above the effect of the weight training alone because estrogens usually maintain bone density, or increase it by only 1-3% over a 1-2 year period. If this is correct, then a minimum of 21 subjects per group will be needed to demonstrate this effect. The numbers will be larger if dropouts are factored into the estimate and/or the standard deviation of the response to either treatment is greater. This might be expected with studies of longer duration and occurred in the study by Notelovitz et al. where 13 subjects dropped out and the SD was 12% in the estrogen-alone group. A smaller effect will be more difficult to demonstrate and will be biologically less meaningful; a larger effect is possible, of course, but seems unlikely. Thus, this study is very difficult to conduct given the difficulties in compliance and the probable small size of any additive effect of weight training plus estrogen.
TABLE1. DESIRED DIFFERENCE (070) BETWEEN WEIGHTTRAINING VERSUSWEIGHTTRAININGPLUSESTROGEN
Assumed standard deviation in response (Yo)
5 7 9
Sample size per group
I
2
3
4
5
6
7
525 1029 1701
131 257 576
58 114 234
33 64 132
21 41 84
IS 29 58
11 21 43
Dr. Ego Seeman Department of Endocrinology Austin Hospital Heidelberg, Melbourne, Australia
709
8
8 16 33
9
1
6 13 26
0
5 10 21
