Elevated PTHrP Associated with Lactation and Bone Density Loss
ABSTRACT & COMMENTARY
Synopsis: The lactating breast secretes a hormone referred to as parathyroid hormone-related peptide (PTHrP) that mobilizes calcium from the maternal skeleton for incorporation into breast milk. PTHrP plays a role in the loss of bone mass associated with lactation.
Source: Sowers MF, et al. JAMA 1996;276:549-554.
Most studies with more than one measure of bone density during the time of actual lactation show that there is bone loss during lactation. After lactation ceases, bone mass accrues. In rats, lactational bone loss is independent of parathyroid hormone and vitamin D levels. Also, there are no differences in calciotrophic hormone levels between lactating and nonlactating women. Thus, it has been suggested that there is another factor mediating calcium mobilization during lactation. The data in the study by Sowers et al suggest that this factor is parathyroid hormone-related peptide (PTHrP), which is synthesized in lactating mammary tissue. This investigation is a prospective, longitudinal study of women who planned to nurse for six months vs. those who did not. Observations, including procurement of blood samples, were made in 115 women at two weeks, two months, six months, 12 months, and 18 months postpartum. Bone mineral density was determined by dual-energy x-ray absorptiometry at the femoral neck and lumbar spine at two weeks, six months, 12 months, and 18 months postpartum. The investigators found that elevated PTHrP values were significantly associated with breast-feeding status, elevated prolactin levels, and lower estradiol levels. Furthermore, PTHrP levels were strongly associated with bone mineral density loss. The authors conclude that suppression of the hypothalamic-pituitary-ovarian axis may not be the only mechanism whereby prolactin is associated with lactational bone loss. Suckling signals the hypothalamus to release oxytocin and prolactin, which in turn may act to stimulate the production and release of PTHrP in the breast.
COMMENT BY SARAH L. BERGA, MD
The present study is yet another example of how women are marvelously engineered to sustain procreation. Apparently, when it comes to physiological processes such as lactation, multiple redundant mechanisms are the rule rather than the exception.
The present study also highlights how expensive reproductive processes can be for the mother. Calcium mobilization is critical for the production of quality breast milk. The hyperprolactinemia of lactation serves not only to suppress hypothalamic-pituitary-ovarian function to create a hypoestrogenic environment to support milk production, it also turns the breast into a classic endocrine gland that is capable of sequestering calcium from maternal bone stores. During pregnancy, the mother’s endocrine system is to some extent supplanted by the placenta, which orchestrates the necessary endocrine milieu needed for fetal growth and development. During lactation, the breast assumes the role played by the placenta. Although the mechanisms by which lactation alters maternal behavior are less well-known and more difficult to study, animal studies suggest that there is cortical activation during suckling and lactation that may well channel awareness and behavioral priorities.
How and to what extent lactation alters appetite, food selection, or other eating behavior in humans is not known. Certainly, however, it is our job as physicians to reinforce nutritional proclivities by suggesting that good nutrition, including adequate calcium, protein, and vitamin D intake, is crucial during lactation. The usual emphasis postpartum is on weight loss, but during lactation the expected trajectory for weight loss may be modified. The authors of this article note that about 600 mL of milk is produced at three months following parturition, which requires 168 mg of calcium per day. At six months, the figures are 1 L of milk and 280 mg of calcium. This means that about 4-5 glasses of milk per day are needed to sustain maternal and infant needs. Whether adequate calcium intake will blunt the bone loss of lactation remains to be established. However, in most instances, given the multiple nutritional, immunological, and emotional benefits of breast-feeding, lactation should be encouraged and supported rather than discouraged, because in general bone lost during breast-feeding will be restored after lactation ceases.
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