Reply to W. Pluskiewicz

We welcome the opportunity to respond to the letter of Prof. Wojciech Pluskiewicz regarding our study; this confirms that the effects of pregnancy on the skeleton are a well explained phenomenon, but that evidence on apparent bone loss is conflicting. A recent paper by Ulrich et al. [1], published after our manuscript was accepted by for publication, agrees with our results, showing that urinary cross-linked type I collagen N-telopeptides (a marker of bone resorption) is not significantly different from controls during the first and second trimesters, significantly increased in the third trimester, and subsequently decreased one to two weeks after parturition. Prof. Pluskiewicz suggests that lactation may have influenced bone loss. Breast-feeding is a well recognized cause of reduction of bone density, particularly when prolonged (more than 6 months [2]); we considered that a postpartum BMD measurement performed as early as two weeks after parturition could not reflect changes possibly related to lactation, so breast-feeding was not controlled for in our subjects. We think that a loss of bone that Prof. Pluskiewicz himself considers to be uncommon in six weeks can hardly be expected to take place in the space of two weeks.

The second point raised by Prof. Pluskiewicz is the BMD variable values that exceed results given usually by other authors. Indeed, the magnitude of bone loss reported in the literature is highly variable, ranging from 0 % to 13 %. This may be accounted for by the heterogeneity of population studied, including the existence of conditions that may have a potential impact on bone mass, the age of the subjects, genetics, etc. Our suggestion is that the high bone turnover that characterizes the third trimester is only partly related to the fetal calcium demands of about 30 g (corresponding to a 3 % bone loss from maternal skeleton, that Prof. Pluskiewicz seems to consider acceptable). It would be reasonable to hypothesize that, besides a loss of calcium, bone mineral redistribution takes place in the maternal skeleton during the last months of pregnancy [3], implying changes in bone anisotropy and connectivity as detected by quantitative ultrasound parameters such as broadband ultrasound attenuation (BUA). In addition, it should be pointed out that BMD measured by DXA can only evaluate areal bone density and gives no information on volumetric and microarchitectural changes. It is theoretically possible that such changes, if present, were given by DXA as quantitative, and that figures obtained correspond more to changes in structure than to real bone loss. This may obviously have some consequences for the significance and the reliability of BMD results. Prof. Pluskiewicz’s advice is to present results in individual subjects. In general, this could be applied to many previous studies on different subjects; however, appropriate statistics should help to estimate the contribution of a single subject to a mean value, especially when individual changes exceeds (as it is the case) the long-term coefficient of variation.

A potential limitation of our study is the lack of data on the behavior of BMD and BUA obtained in the first 12 - 18 months after parturition. We are following up some subjects in our study in order to evaluate BMD and BUA changes following normal pregnancy; we expect to finish the study in a small number of subjects, given the low compliance to such investigations.

In a very low number of subjects, it is mandatory to give individual changes only that are greater than 21 times the long-term in vivo precision; the advice offered by Prof. Pluskiewicz is reasonable, and will contribute to interpretation of the phenomena we intend to observe.

References

• 1 Ulrich U, Miller P B, Eyre D R, Chesnut C H, Schlebusch H, Soules M R. Bone remodelling and bone mineral density during pregnancy.  Arch Gynecol Obstet. 2003;  268 309-316
• 2 Sowers M, Corton G, Shapiro B, Jannausch M, Crutchfield M, Smith M L. Changes in bone density with lactation.  JAMA. 1993;  269 3130-3135
• 3 Naylor K E, Iqbal P, Fledelius C, Fraser R B, Eastell R. The effect of pregnancy on bone density and bone turnover.  J Bone Min Res. 2000;  15 129-137