Changes in Bones

The increase in bone mass during growth results from an increase in bone size, not bone density (bone mass per unit volume). After growth stops, the bones continue to increase slowly in girth (except the mandible, which gets smaller). However, between ages 40 and 50, bone density begins to progressively decrease. This decrease occurs because bone is lost from within. Bone cortices become thinner from the inside; also, whole structural elements of cancellous bone are removed, a process that differs in detail between the central and peripheral skeletons. Interestingly, decreased bone density does not tend to result from decreased bone production; bone remodeling can actually increase with aging.

Bone loss that occurs as part of normal aging can be divided into 2 mechanisms: a rapid one that affects women after menopause (menopausal bone loss) and a slow one that affects both women and men after age 40 to 50 (senescent bone loss). These 2 mechanisms have distinct histologic and clinical features (see Table 48-1); however, in women, the 2 mechanisms eventually overlap and become difficult to differentiate. Senescent bone loss may also overlap with secondary hyperparathyroidism, which may result from the aging intestine's impaired ability to absorb calcium, and with relative hypercortisolism. Sarcopenia, inactivity, and reduced mechanical loading also contribute. Clinical bone loss is usually multifactorial.

The extent to which the 2 mechanisms contribute can vary significantly among aging individuals. This variability is one reason why therapies that target only 1 of the mechanisms produce results that vary among elderly individuals.

Menopausal bone loss: Before menopause, sex hormones protect the bone, at least in part, by regulating the production, development, and death (by apoptosis) of osteoclasts and osteoblasts. Sex hormones may also protect the bone by regulating production of cytokines and responsiveness of bone marrow cell progenitors to cytokines. For example, sex hormones inhibit production of cytokines IL-1, IL-6, and tumor necrosis factor. Overproduction of these cytokines increases osteoclast production and thereby increases bone resorption, which is largely responsible for menopausal bone loss. The same cytokines are involved in pathologic bone resorption that occurs in several disorders, including multiple myeloma, Paget's disease, rheumatoid arthritis, Gorham-Stout or disappearing bone disease, hyperthyroidism, primary and secondary hyperparathyroidism, and McCune-Albright syndrome.

Sudden loss of sex hormones causes bone loss to increase up to 10-fold. In women, estrogen declines precipitously at menopause, causing rapid bone loss during the next 5 to 10 yr (menopausal bone loss). In men, testosterone production normally declines gradually, so bone loss is linear and slow. However, in men who undergo castration, the abrupt cessation of testosterone production results in rapid bone loss. Sex hormone deficiency seems to delay osteoclast apoptosis but promotes osteoblast apoptosis, increasing bone resorption relative to bone formation. Delayed osteoclast apoptosis may also deepen resorption cavities, resulting in trabecular perforation characteristic of estrogen deficiency.

Senescent bone loss: The amount of bone formed during remodeling decreases with aging in both sexes, causing a consistent decrease in wall thickness, especially in trabecular bone. Aging decreases osteoblast and new bone formation, decreases bone mineral density, and increases adipocyte formation in the bone marrow. Vitamin D likely plays a role in inhibiting osteoblast apoptosis; therefore, vitamin D deficiency may result in a decrease in the number of osteoblasts and thus contribute to the age-related decrease in bone formation.

Pathologic factors: Loss of bone mass in either sex may accelerate because of high circulating levels of endogenous or exogenous glucocorticoids and thyroxine, alcoholism, prolonged immobilization, gastrectomy, malabsorption, hypercalciuria, some types of cancer, and cigarette smoking.

Consequences: Bone mass decreases in the axial (primarily cancellous) and appendicular (primarily cortical) skeletons. In cancellous bone, trabeculae thin or are destroyed. Cortical bones thin and become more porous.

Increased bone loss causes loss of height (stooping) and dorsal kyphosis (dowager's hump). Decreased bone density and microarchitectural bone deterioration increase the susceptibility of bone to fractures, a condition known as osteoporosis . Conventionally, osteoporosis is diagnosed when bone density is at least 2.5 standard deviations below the young adult mean; when bone density is between 1 standard deviation and 2.5 standard deviations below the young adult mean, the condition is termed osteopenia. Because women accumulate less skeletal mass than men during their growing years (particularly during puberty), resulting in smaller, narrower, more fragile bones with thinner cortices, and because women undergo menopausal bone loss, women are at higher risk for osteoporosis and osteopenia.

Purely menopausal bone loss increases risk of vertebral and Colles' fractures disproportionately. Purely senescent bone loss increases risk of vertebral and hip fractures disproportionately. However, in clinical practice, determining the relative contributions of the type of bone loss to the development of a fracture is difficult and usually not helpful. In general, the elderly typically develop fractures in the spine or proximal long bones (eg, hip fractures) secondary to minimal forces; this contrasts with younger adults, who often develop fractures in the middle of bones secondary to maximal forces.

This topic was last updated May 2005.