OSTEOPOROSIS

Osteoporosis is a reduction in bone mass and weakening of bone architecture that increases the susceptibility of bone to fracture. Bone is a living tissue that is constantly being broken down and resynthesized at 1 to 2 million microscopic sites in the adult skeleton. Osteoporosis occurs when the rate of breakdown is faster than the rate of resynthesis.[1]

Osteoporosis occurs in both sexes but is more frequent in women after menopause. One measure of susceptibility to fracture is bone mineral density (BMD), which is measured by X-ray absorption. The results are given (for women) in terms of the decrease in density from that of the average 35-year-old. The decrease in BMD and its relation to fracture applies to the whole population of women and does not tell whether an individual will have a fracture, only that they are in a population of higher risk.

It is important to realize that BMD is only one of many risk factors for fracture: others include “smoking, early menopause, lack of physical exercise, especially weight-bearing exercise, family history, personal history of fracture, a tendency to fall, and alcohol abuse” as well as glucocorticoid use.[2] On the other hand, physical activity increases bone mass, density, and strength and can improve balance and coordination even in old, frail people.[3]

The site of fracture is important in terms of consequences: hip fractures cause more severe and long-term problems than those of arms, back (vertebral), or wrist, yet the drugs available have greater effectiveness at these latter sites. The patient needs to take into account the drug’s risks, as described in the drug profiles below, along with a possible benefit. This is especially true for vertebral fractures that are often used to measure the efficacy of a drug yet are frequently unaccompanied by any symptoms.

The history of the treatment or prevention of osteoporosis is strewn with drugs such as estrogens—discussed below—and others in this chapter with marginal effectiveness or with risks clearly outweighing the benefits.

For the last several decades, much attention in the osteoporosis field has been lavished on the acclaimed ability of hormone replacement therapy (HRT) to prevent osteoporosis. In 1991, Public Citizen’s Health Research Group wrote, “Female replacement hormones may someday be remembered as the most recklessly prescribed and dangerous drugs of this century.”[4] In 2002, the results of the Women’s Health Initiative (WHI), a large, long-term, clinical trial sponsored by the National Institutes of Health, finally confirmed that the risks of hormone replacement therapy (HRT) outweighed its benefits.[5]

The WHI trial enrolled 27,000 healthy postmenopausal women between 1993 and 1998 with the goal of seeing whether HRT would help prevent heart disease and hip fractures. The trial was divided into two parts: 11,000 women with a previous hysterectomy were randomized to get either estrogen alone or a placebo; 16,600 women were randomized to get estrogen plus medroxyprogesterone (or a commercially available combination of the two with the brand name Prempro) or a placebo. The trial was originally scheduled to conclude in 2005, but both parts were stopped early because of the increase in serious adverse events.

In the estrogen plus medroxyprogesterone arm, the main reason for stopping the trial early was an increased risk of invasive breast cancer in women receiving HRT, as opposed to those on placebo. This risk, combined with an increase in adverse cardiovascular events, such as increased coronary heart disease, stroke, and pulmonary embolism that began in the first year of HRT treatment, outweighed the benefit of an increase in BMD and a decrease in hip fractures. A later analysis of the WHI study found that there was no benefit with HRT even in the subgroup of women considered to be at high risk of fracture.[6]

In the estrogen-alone part of the trial (in women who had had a hysterectomy and thus were not at risk for uterine cancer, which can be caused by estrogen), the main reason for stopping was the lack of an effect on heart disease (either increase or decrease), the major question being evaluated. The increased risk of stroke outweighed the benefit of a decrease in hip fracture risk.[7] Thus, neither estrogen alone nor estrogen combined with progesterone is now recommended for prevention of osteoporosis.

The mainstays for decreasing the risk of postmenopausal osteoporosis are weight-bearing exercise and adequate calcium and vitamin D intake. Regular exercise, particularly weight bearing, is most protective and can be as simple as daily walking and climbing stairs. On average, postmenopausal women require 1,500 milligrams per day of elemental calcium. Vitamin D supplementation of 400 to 800 international units (IU) per day may also be required to ensure adequate daily intake in postmenopausal women. See our profiles of calcium and  Vitamin D for more information on supplementation, as well as the section on vitamins and minerals.

Some of the best sources of calcium are dietary. The following table lists the elemental calcium content, in milligrams, of some common foods.[8]