Texas Institute for Reproductive Medicine & Endocrinology
Osteoporosis is a disease characterized by low bone mass and disruption of the bone tissue microarchitectural structure resulting in enhanced bone fragility, and a consequent increased fracture risk.
The World Health Organization (WHO) has developed specific criteria for the degrees of bone density decrease and the attendant fracture risk based on bone densitometry studies.The term Osteopenia is defined as a bone mineral density between 1 and 2.5 standard deviations below the young adult mean value. Osteoporosis is defined as a bone mineral density more than 2.5 standard deviations below the young adult mean normal. Bone density has a genetic component
Three distinct genetic factors contribute to fracture risk. First, peak bone mass occurs between ages 30 and 35. Second, after about age 35, bone mass decreases over time and fracture risk increases. The decrease of bone density is exacerbated by the loss of estrogen after menopause in women, a genetically determined event. Third, the genetically determined length of the femoral neck correlates with fracture risk, people with a longer femoral neck having an increased fracture risk.
Daughters of women with osteoporosis have been noted to have reduced bone mass in the spine and probably also in the femoral neck that would put them at increased fracture risk. This reduced bone mass probably results from a low peak bone mass rather than from excessive bone loss. In both women and men, interestingly, a low peak bone mass may be genetically associated with premature graying of the hair.
Apart from genetic factors, physiologic factors and environmental considerations are also important in putting people at risk for osteoporosis.
Bone is a living tissue. It serves as a storage site for calcium as well as structural material for the skeleton. Hormones regulate the ebb and flow of calcium in and out of bone. Bone is constantly remodeled by the actions of two systems, the osteoclasts that remove bone and the osteoblasts that make new bone. The osteoclasts are derived from macrophages and function to digest trenches within the bone in periodic cycles of activity. These trenches are then filled in with new bone produced by osteoblasts. When the amount of bone being removed by the osteoclasts exceeds the amount put back by the osteoblasts, the bone mass is reduced and eventually becomes increasingly subject to fracture. Sex steroids, estrogen in women and testosterone in men, act to limit osteoclast function to allow as much bone to be replaced as removed. When sex steroids are absent, such as in menopause or other hypogonadal states, osteoclast activity is greater than osteoblast activity and the result is a net loss of bone. In women going through menopause, this leads to a rapid decrease in bone mass during the 4-5 years after menopause with a slowed rate of bone loss thereafter.
Sex Hormone Deficiency
The most common cause of osteoporosis (bone loss) in women is cessation of female hormone production. Menopause is the most dramatic cause of estrogen loss. In women, menopause occurs at about age 51 and is associated with a significant loss of bone mass unless hormone replacement therapy is started and continued.
It is of interest that the final common pathway in maintaining bone mass in men is also via the estrogen receptor. In men, male hormones are converted in part to estrogen. Estrogen appears to be important in keeping osteoclast function suppressed.
Dietary factors, such as low vitamin D and calcium content, related to an American diet, may be an important contributing factor to osteoporosis. In some studies, when vitamin D supplements and calcium were added to the diet of elderly nursing home residents, there was a decreased incidence of hip fracture. Other studies using randomly selected patients did not show improvement with vitamin D alone. This indicates that by selecting the population that would most benefit, one may be able to target specific therapy to groups of patients most likely to respond.
Sunny climes, such as Houston, generally provide sufficient Vitamin D through sun exposure, but shut-ins and nursing home residents may not have this benefit and may need dietary evaluation for supplemental Vitamin D needs. Vitamin D rich foods include fortified milk, fatty fish, egg and egg yolk (but watch cholesterol!). In at risk patients, recommended daily Vitamin D supplementation is about 200 to 400 IUs daily but no more than 800 without medical consultation.
CALCIUM AND EXERCISE
Calcium, along with exercise, is important to the attainment of the genetically determined peak bone mass that occurs in women between the ages of 30 and 35. In menopausal women who only exercise, bone loss continues while in women who exercise and take calcium supplementation, bone mass stabilizes. Calcium and exercise are better than exercise alone, but not as good as estrogen replacement.
Very large amounts of exercise in women will cause hypothalamic dysfunction resulting in irregular cycles, low estrogen levels, and low bone mass with an increased risk of osteoporosis. On the other hand, physical inactivity among the elderly is considered a major risk for hip fracture. Exercise in the elderly can compensate for decreased muscle strength and may help prevent progression of osteoporosis, especially in the hip. In addition, exercise in the elderly may modestly decrease the incidence of falls by improved muscle tone.
Calcium supplements are often needed and are available over the counter. These supplements should generally be given with meals in divided doses.
Smoking is a significant risk factor for osteoporosis. Men and women who were smokers had significantly reduced bone density in the hip in proportion to the amount smoked. With the increasing number of women already at risk for osteoporosis engaging in smoking, the already high risk of osteoporosis will be increased significantly. The reason for this increased risk of osteoporosis may be that women who smoke have an earlier menopause by about 2 years, and therefore may increase the rate of bone loss earlier. In addition, smokers weigh less than non-smokers which also increases the risk of osteoporosis.
The only apparent advantage to obesity may be the lower risk of osteoporosis. Fat tissue converts weak androgens from the adrenal into estrogens that help maintain bone mass. Another factor is that increased stress on the skeleton and more calcium intake may account for the higher bone mass.
Long term use of high dose glucocorticoids or thyroid hormone at supraphysiologic doses is associated with osteoporosis. Fractures on high dose glucocorticoids may occur even at relatively greater bone mineral density values, indicating possible impairment in normal bone support structures.
People who use large amounts of alcohol may have lower bone mineral densities than those who do not. Alcohol appears to poison the osteoblast, and thereby reduce the amount of bone refill that occurs with the bone remodeling cycle. In addition, long term alcohol use is associated with nutritional disorders with reduced amounts of vitamin D and calcium. There remains controversy however, as a recent epidemiological study found that alcohol was not a significant risk factor for osteoporosis. Alcohol abuse often increases the risk of falls and thereby contributes to fracture, especially if osteoporosis is also present.
A 1995 major study by Cummings et al. followed 9516 white women over age 65 for over 4 years and concluded that a family history of hip fracture was the major risk factor for hip fracture in the patient group with a relative risk of 2.0 indicating the dominance of a genetic factor. Other significant risk factors were previous fracture, being tall at age 25, hyperthyroidism, use of certain medications, high caffeine intake, lack of mobility, and visual impairment. Weight gain since age 25 was associated with a lower risk of osteoporosis.
Up to 25 million Americans are affected by osteoporosis. One of every two women over the age of 50 and one of five men over age 50 will develop an osteoporotic fracture in their lifetime. Each year, there are 1.5 million osteoporotic fractures of the hip, spine and wrist.
The first manifestation of osteoporosis is usually a fracture. The only simple technique for detection of increased risk of bone fracture secondary to osteoporosis is through bone densitometry studies. Since a variety of conditions other than menopause may also result in osteoporosis, bone densitometry would be expected to establish the diagnosis of osteoporosis in many more people than only those with menopause.
Osteoporosis is one of the three common silent killers that have plagued modern civilization. The first, hypertension, almost always remains without symptoms until a stroke, heart attack or renal failure occurs. A simple blood pressure cuff measurement can detect the disease and lead to effective therapies that can prevent the adverse outcomes. The second, elevated LDL cholesterol, silently clogs arteries starting in young adulthood. This process may eventually choke off the vital supply of blood to organs throughout the body leading to heart disease, peripheral vascular disease, strokes, and renal failure. A simple blood test for the bad LDL cholesterol and the good HDL cholesterol can determine to a great extent who is at risk and who can benefit from preventive therapy. The third disorder in this series is osteoporosis. The superstructure of bone is quietly eaten away and over time the bone weakens and is subject to fracture.
THE IMPACT OF OSTEOPOROSIS.
Vertebral fractures cause loss of height, kyphosis, back pain, and significant changes in life style.
Hip fractures are associated with up to a 20% mortality over the several months following the fracture due to deep venous thrombosis, pneumonia, and pulmonary embolism. About 60% of those that survive require help with activities of daily living. Up to 20% require long-term institutionalization in extended care facilities and only about 20% have complete return of function. instead.
It has long been reported that osteoporosis is mainly a disease of older white women. It is clear this myopic view will miss the large number of aging minority groups that develop osteoporotic fracture, as well as the significant number of men that develop osteoporotic fracture.
Calcium replacement therapy, Vitamin D and exercise can help maintain bone mineral density in many patients. This is especially important in childhood and young adulthood in order to achieve the limit of peak bone mass dictated by genetics.
In women, bone loss is most severe with estrogen deficiency. With the average age of natural menopause at about 51 years, significant bone loss becomes problematic within 4-5 years at the time of menopause. This bone loss can be prevented in large part by early recognition of the menopausal state, and treatment with estrogen replacement therapy. The benefits of estrogen replacement last for as long as estrogen is given. Bone loss will resume rapidly once estrogen therapy has been stopped. In postmenopausal women who still have a uterus, estrogen must be combined with a progestin to prevent the possible development of endometrial cancer. In women with a uterus on estrogen only, there is a 20% chance of developing endometrial hyperplasia at one year and a 60% chance after 3 years. Since different progestins have different physiological properties, the choice of a progestin may be significant in some patients.
In men with hypogonadal disorders, replacement therapy with testosterone maintains bone mineral density for as long as testosterone is used.
Calcitonin is an important option for many women with established osteoporosis. In women with bone pain from osteoporosis, calcitonin may act on the pain pathways and reduce pain. It prevents the loss of trabecular bone in the spine and appears to have little effect on femoral cortical bone loss.
A class of compounds called bisphosphonates can be given orally and enters into the bone where it inhibits the action of osteoclasts, resulting in less bone loss. The bisphosphonates approved for use in the US are alendronate (Fosamax) and risedronate (Actonel).
There is one treatment option that can actually significantly increase bone mass. Sodium fluoride will stimulate new bone formation, but the bone formed is unusually brittle and can result in cracks in the bone substance. Fluoride treatment is considered experimental and is associated with significant side effects. It can be considered in severe osteoporosis where other options are not available.
In addition to direct medical costs, many of those affected by osteoporotic fracture are caregivers for spouses, parents, children and grandchildren. After osteoporotic fracture, many of these caregivers become care-receivers and drain the economy of their much needed help. The annual direct and indirect costs of osteoporosis to the health care system have been estimated at $18 billion dollars in 1993 with $7 billion of that attributed to hip fracture
As the population ages, osteoporosis will become an epidemic in the next 20 years. Caregivers will become care-receivers as osteoporotic fractures take their toll. The economic and human costs will present a major challenge for the children of the present as they become members of the work force and are compelled to support their parents and grandparents. Society must be proactive, not reactive with a problem of this scope. Since therapy is effective if started before fracture occurs, high risk groups, such as menopausal women not on hormone replacement, should be informed of their bone density to allow them to decide with their physicians on therapy options.
For more general details on osteoporosis see Osteoporosis under "Patient Care" on the TIRME home page.