Or No Decline in Bone Mass (2002)

To the Editor: Drs. Barker and Blumsohn suggest that our study in the July issue of JBMR1 does not provide sufficient evidence to show that obese premenopausal women who lose weight do not lose bone and that those women who are supplemented with calcium during weight loss tend to gain bone. We disagree and would like to confirm why our data support our original conclusions.1 Drs. Barker and Blumsohn suggest that −0.2% ± 2.8% change in lumbar bone mineral density (LBMD) in the placebo (Pla) group over 6 months implies that the 95% confidence limit is 3.5% (loss) over 1 year. Whereas it is not unusual to talk about bone loss in terms of an annualized rate, it is problematic to extrapolate the findings from a 6-month weight-loss study to a full year, because the rate of change will not necessarily remain constant. Although it is possible that the LBMD loss is as dramatic as 1.8% over 6 months (95% CI of −0.2% ± 1.6%), it is also possible that there is a gain of 1.4% bone. We used the conservative statistical approach of hypothesis testing to conclude that LBMD change in the Pla weight loss group did not differ significantly from zero. Importantly, and similar to the findings in the Pla group, there was no significant reduction in BMD in the weight maintenance group (WM; −0.8% ± 1.9% and −0.1% ± 1.3 for lumbar and whole body, respectively). However, in a different weight loss study in this laboratory that used similar methods and level of obesity but used postmenopausal women, we were able to detect a significant loss of BMD compared with the WM group.2 Consistent with this, a recent study3 including both pre- and postmenopausal obese women showed bone loss with weight loss. Furthermore, weight reduction may be associated with bone loss in nonobese premenopausal women, as shown in the well-controlled study by Salamone et al.4 In contrast, our population of obese premenopausal women shows no bone loss.1 Our published article1 shows that calcium supplementation tends to increase LBMD in the weight loss group compared with Pla and WM (analysis of variance [ANOVA]; p = 0.052). The linear contrast analysis in the SuperANOVA statistical program (SAS Institute, Cary, NC, USA) shows that the difference in LBMD change (%) between the Ca and Pla groups has a p value of 0.063 (this was considered a trend). Although SAS technical support advised us that the linear contrast in the program performs a Scheffé test, we have determined that the output is consistent with Fisher's protected least significant difference (LSD) test and therefore, our description of analysis should be amended. We appreciate the efforts by Drs. Barker and Blumsohn in noting this discrepancy; but our conclusions remain the same. The protected LSD test is a better choice than the Scheffé test because it has more power, yet controls for type I errors (false positive) and is especially appropriate for comparisons between 2 and 3 groups when sample sizes are relatively equal,5 as in our case (n = 14 in both the Ca and Pla groups).1 Although a paired t-test shows that the increase in LBMD within the Ca group is significant (p = 0.025), this approach is considered less conservative and therefore we reported the trend from the ANOVA and posthoc tests.1 In addition, our biochemical data1 does not show a significant suppression in bone turnover for Ca supplementation compared with Pla. Taken together, there can be no change in our original interpretation of the data, which shows only a trend for the Ca group to increase LBMD. We agree with Drs. Barker and Blumsohn that dual energy X-ray absorptiometry (DXA) may not be ideal for measuring changes in bone density during weight loss due to large changes in body thickness and composition. DXA accuracy is an ongoing concern in the weight loss field,6-8 and therefore our study was designed to include serial measurements of bone turnover and serum parathyroid hormone (PTH) to complement these observations. Hence, we tend to be conservative in our interpretation of any DXA bone data due to weight loss, and use all the available information (including biochemical markers) to draw conclusions. Drs. Barker and Blumsohn are unclear about “the status of the weight maintenance group.” As carefully described in both the Protocol and Results sections of the published article, the weight maintenance group was not prospectively included in this study. Indeed, our current studies are addressing this group in a prospective manner. There was concern for “major differences in dietary composition between the groups” due to our reported higher dietary intake of calcium in the Ca compared with the Pla group. It is possible that a higher dietary Ca, as well as supplemental Ca may have contributed to our findings. As Drs. Barker and Blumsohn suggest, it is also possible that intake of other nutrients were slightly different between these groups, but it should be noted that too much emphasis on reported dietary intake is inappropriate in clinical obesity trials due to inaccurate reporting.9 This is a reason why these studies were designed to examine body weight rather than reported calorie or nutrient consumption, as a final outcome variable. Drs. Barker and Blumsohn state that “urinary makers of bone resorption are difficult to interpret when expressed as a ratio to creatinine excretion.” We agree that creatinine excretion may change due to alterations in diet and muscle mass. However, there were two groups losing weight (Ca and Pla), and only one group (Pla) showed a trend to increase deoxypyridinoline (DPD)/creatinine excretion. Furthermore, if creatinine excretion decreased in response to diet, it would be expected that both measurements normalized for creatinine (DPD and pyridinoline) would increase with weight loss (WL), but this was not observed. In addition, neither WL group lost more lean mass compared with the weight maintenance group. To further support our original conclusions, a subset of available samples (n = 14 subjects before and after weight loss) was measured, and we found that 24-h creatinine excretion in subjects who lost weight (WL; n = 5 Ca and n = 4 Pla) was not significantly different than those who did not lose weight (n = 5; two-way ANOVA). Due to the limited number of samples, we also estimated creatinine excretion from lean mass10 in all the subjects (n = 38) at both time points. These calculated data also showed that the groups did not respond differently due to diet. Hence, we are unable to show a change in creatinine excretion with this modest weight loss. Yet, we think this is an important issue that warrants further study, and is currently being addressed in our laboratory. Although there are certain limitations to the original study, which we highlighted in all material respects in the article, we would like to reaffirm that this study shows no bone loss with weight loss (acknowledging DXA measurement limitation) and that increased Ca intake shows a trend to increase LBMD. This is the first study to examine weight loss and bone in a homogenous population of obese premenopausal women including two levels of Ca intake. As expected from any single intervention study, there are many questions that arise from these data, and a larger clinical trial is indicated to confirm and/or expand these findings.