Female reproductive system and bone

Abstract

The female reproductive system plays a major role in regulating the acquisition and loss of bone by the skeleton from menarche through senescence. Onset of gonadal sex steroid secretion at puberty is the major factor responsible for skeletal longitudinal and radial growth, as well as significant gain in bone density, until peak bone density is achieved in third decade of life. Gonadal sex steroids then help maintain peak bone density until menopause, including during the transient changes in skeletal mineral content associated with pregnancy and lactation. At menopause, decreased gonadal sex steroid production normally leads to rapid bone loss. The most rapid bone loss associated with decreased estrogen levels occurs in the first 8-10 years after menopause, with slower age-related bone loss occurring during later life. Age-related bone loss in women after the early menopausal phase of bone loss is caused by ongoing gonadal sex steroid deficiency, vitamin D deficiency, and secondary hyperparathyroidism. Other factors also contribute to age-related bone loss, including intrinsic defects in osteoblast function, impairment of the GH/IGF axis, reduced peak bone mass, age-associated sarcopenia, and various sporadic secondary causes. Further understanding of the relative contributions of the female reproductive system and each of the other factors to development and maintenance of the female skeleton, bone loss, and fracture risk will lead to improved approaches for prevention and treatment of osteoporosis.

Figure 1

The STRAW staging system, showing the relation between alterations in cycle regularity and endocrine changes across the various stages of reproductive aging. (Reproduced from Soules MR, Sherman S, Parrott E, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil Steril 2001;76:874–878; with permission.)

Figure 2

Endocrine fluctuations and follicle growth in the menstrual cycle. (Reproduced from Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences. Endocrine Rev 2009;30:472; with permission.)

Figure 3

Diagrammatic representation of how the various hormones interact at the ovary, pituitary, and hypothalamus, with feedback loops.

Figure 4

Patterns of age-related bone loss in women and men. Dashed lines represent trabecular bone and solid lines, cortical bone. The figure is based on multiple cross-sectional and longitudinal studies using DXA. (Reproduced from Khosla S, Riggs BL. Pathophysiology of age-related bone loss and osteoporosis. Endocrinol Metab Clin N Am 2005;34:1017; with permission.)

Figure 5

(A) Values for vBMD (mg/cm³) of the total vertebral body in a population sample of Rochester, Minnesota, women and men between the ages of 20 and 97 years. Individual values and smoother lines are given for premenopausal women in red, for postmenopausal women in blue, and for men in black. (B) Values for cortical vBMD at the distal radius in the same cohort, with color code as in (A). All changes with age were significant (P <.05). (Reproduced from Riggs BL, Melton LJ 3^rd, Robb RA, et al. A population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res 2004;19:1950; with permission.)

Figure 6

Age-specific incidence rates for proximal femur (hip), vertebral (spine), and distal forearm (wrist) fractures in Rochester, Minnesota, women (A) and men (B). (Adapted from Cooper C, Melton LJ. Epidemiology of osteoporosis. Trends Endocrinol Metab 1992;3:225; with permission.

Figure 7

Summary of stimulatory and inhibitory factors involved in osteoclast development and apoptosis. (Reproduced from Quinn JMW, Saleh H. Modulation of osteoclast function in bone by the immune system. Mol Cell Endocrinol 2009;310:42; with permission.)