BoneKEy-Osteovision | Perspective
Conversations between breast and bone: Physiological bone loss during lactation as evolutionary template for osteolysis in breast cancer and pathological bone loss after menopause
John J Wysolmerski
DOI:10.1138/20070268
Abstract
Reproduction in mammals is associated with an impressive cycle of bone loss and repair. Lactating mothers lose bone rapidly to supply calcium for milk production. After weaning, bone mass recovers almost as quickly as it was lost. This phenomenon had been well described for many years, but recent studies have begun to paint a clearer picture of the hormonal and molecular regulation of this transient skeletal demineralization. Bone loss occurs as the result of a coordinated conversation between the breast and bone. Suckling induces hypothalamic hypogonadism and the lactating breast secretes parathyroid hormone-related protein into the circulation. Low estrogen levels and elevated PTHrP levels act in combination to liberate skeletal calcium stores. Calcium then feeds back on the breast via the calcium-sensing receptor to regulate calcium transport into milk and PTHrP production, defining a feedback loop between breast and bone. When lactation ends, bone resorption is suddenly halted, but little is currently known of the mechanisms that mediate bone recovery after weaning. These alterations in bone and mineral metabolism during the reproductive cycle are descendants of ancient adaptations that evolved to support egg production in lower vertebrates. Therefore it is interesting to consider if pathological bone resorption in patients with breast cancer and in post-menopausal women may represent the accidental reactivation of circuitry designed to supply calcium for milk production. A better understanding of the skeletal response to weaning may offer clues to new therapies for bone disease.
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