Clinical Approach

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Osteoporosis is an important health issue because the resultant bone fractures cause a great deal of morbidity in chronic pain, loss of independence, and loss of function, as well as mortality. Risk factors for the development of osteoporosis include a low peak skeletal density reached in young adulthood, increasing age, loss of steroid hormone production (menopause or hypogonadism), smoking, nutritional deficiencies, and genetically low bone density. Approximately 14% of white women and 3-5% of white men will develop osteoporosis in their lifetime. The prevalence is lower in other ethnic groups.

Osteoporosis can be either idiopathic or a manifestation of another underlying disease process. Probably the most common form of secondary osteoporosis is caused by glucocorticoid excess, usually iatrogenic steroid use for an inflammatory disease such as rheumatoid arthritis. Patients, both men and women, with rheumatoid arthritis are susceptible to accelerated bone loss with even low doses of glucocorticoids. Gonadal deficiency is another common cause, which is seen physiologically in menopausal women but is seen pathologically in women who are amenorrheic (e.g., female athletes such as gymnasts or marathon runners) or as a result of hyperprolactinemia. Men with gonadal failure for whatever reason also are prone to develop osteoporosis.

Osteoporosis is a common feature of several endocrinopathies. Patients with hyperparathyroidism will develop osteoporosis because of increased calcium mobilization from bone. Long-standing hyperthyroidism, either naturally occurring, as in Graves disease, or as a result of excessive replacement of levothyroxine in patients with hypothyroidism, will also lead to accelerated bone loss. Malnutrition and nutritional deficiencies are causative and are often seen in patients with malabsorption; for example, most patients, both men and women, with celiac sprue have osteoporosis. Certain medications, such as cyclosporine, antiepileptics, heparin, and gonadotropin-releasing hormone (GnRH) inhibitors, among others, may accelerate bone loss.

Peak bone density occurs in young adulthood under the influence of sex steroid hormone production. Other influential factors include genetics, which may account for 80% of total bone density, adequate calcium intake, and level of physical activity, especially weight-bearing activity. The type of bone growth at this stage is called modeling. After skeletal maturation is reached, the bone growth enters a new phase, termed remodeling, in which repairs are made to damaged bone, existing bone is strengthened, and calcium is released to maintain serum levels under the influence of estrogens, androgens, parathyroid hormone, vitamin D. and various cytokines and other hormones. The activity of the osteoclasts approximates the activity of the osteoblasts in that overall bone density remains stable. However, after age 35 years, bone breakdown begins to exceed bone replacement, and this increases markedly after menopause as a consequence of increased osteoclast activity.

Diagnostic Approach

The benefits and costs of universal screening for osteoporosis are unclear. Rather, a targeted approach is advocated. Those with a family history or other risk factors should be offered screening, as well as patients undergoing a chronic drug (steroid) therapy that may lead to osteoporosis. Currently, all women older than 65 years or those who have sustained a fracture before age 65 years are recommended to undergo BMD testing. Dual-energy x-ray absorptiometry (DEXA scan) is the technique used to define diagnostic thresholds; however, whether the hip, spine, or forearm is the best site for screening is not clearly established. DEXA scan results can be expressed as a Z score, which compares BMD to that in persons of the same age, and a T score, which compares to the young adult normal range. T scores are more useful for predicting fracture risk. Every 1 SD decrease in BMD below the mean doubles the fracture risk. As mentioned, osteoporosis is defined as a T score of-2.5 SD.

Other laboratory evaluations should routinely be considered in patients with osteoporosis. The serum levels of calcium, phosphorus, and alkaline phosphatase should be normal in patients with osteoporosis, although the alkaline phosphatase level sometimes is mildly elevated in the presence of a healing fracture. Laboratory abnormalities should prompt consideration of alternative diagnoses for the bone disease: hypercalcemia in hyperparathyroidism or hypocalcemia in osteomalacia.

If a patient suffers a pathologic fracture, that is, one with minimal trauma, other diagnoses must be excluded. Osteomalacia is defective mineralization of bone matrix with accumulation of unmineralized osteoid and is most often caused by vitamin D deficiency or phosphate deficiency. Patients with osteomalacia frequently have diffuse bone pain and tenderness, proximal muscle weakness, and laboratory abnormalities such as elevated alkaline phosphatase level and low or low to normal calcium level. In the absence of fractures, patients with osteoporosis should have no bone pain or laboratory abnormalities. Both of these disease processes can coexist. A less common bone disease is Paget disease, which is characterized by disorganized bone remodeling with a high alkaline phosphatase level causing weakened and enlarged bones with skeletal deformities. Other important causes of pathologic fracture that must be considered include malignancy, such as multiple myeloma or metastatic disease, and vertebral osteomyelitis.

Treatment

Treatment takes a multifaceted approach. Adequate calcium intake, 1000-1200 mg/d for premenopausal women and adult men to prevent bone loss, and 1500 mg with 400-800 IU of vitamin D per day for postmenopausal women lead to decreased fractures. Estrogen replacement can increase bone density and reduce fracture, as can the use of bisphosphonates, both in combination with calcium and vitamin D. Bisphosphonates can lead to severe esophagitis and must be used with caution in individuals with gastric reflux disease. Bisphosphonates should be taken on an empty stomach, with a large quantity of water, and the patient should remain in the upright position for at least 30 minutes. Selective estrogen receptor modifiers are used for treatment of osteoporosis as well.

Weight-bearing physical activity decreases bone loss and improves coordination and muscle strength, which may prevent falls. Ensuring that patients can see adequately, that they use a cane or walker if needed, that throw rugs are removed, that patients have railings to hold on to in the shower or bath, or that they wear hip protectors can further decrease the risk of life-altering bone fractures.

Comprehension Questions

[51.1] Which of the following patients is most likely to be a candidate for bone mineral density screening?

A. A 65-year-old. thin, white woman who smokes and is 15 years postmenopausal

B. A 40-year-old white woman who exercises daily and still menstruates

C. A healthy 75-year-old white man who is sedentary

D. A 60-year-old overweight African-American woman

E. A 35-year-old asthmatic woman who took prednisone 40 mg/d for a 2-week course I week ago.

[51.2] During which of the following periods in a woman's life is the most bone mass accumulated?

C. Ages 3545

[51.3] A 60-year-old woman presents with the results of her DEXA scan. She has a T score of -1.5 SD at the hip and -2.5 at the spine. How do you interpret these results?

A. She has osteoporosis at the spine and osteopenia at the hip.

B. She has osteoporosis in both areas.

C. This is a normal examination.

D. She has osteoporosis of the hip and osteopenia at the spine.

E. You need to know the Z score.

[51.4] You see a 70-year-old woman in your office for a routine checkup, and you order a DEXA scan for bone mineral density screening. The T score returns as -2.5 in the spine and -2.6 for the hip. Which of the following statements is most accurate?

A. This patient has osteopenia.

B. Estrogen replacement therapy should be started with an anticipated rebuilding of bone mass to near-normal within 1 year.

C. Swimming will help build bone mass.

D. Bisphosphonates would reduce the risk of hip fracture by 50%.

Answers

[51.1 J A. Of the choices, this woman is the only individual with risk factors. Risk factors include white race. age. postmenopausal status, smoking, positive family history, poor nutritional status, and chronic treatment with a drug known to predispose to bone loss.

|51.2] A. The time of greatest accumulation of bone mass in women is during adolescence.

[51.3] A. The T score is the number of standard deviations of a patient's bone mineral density from the mean of young, adult, white women. It is the standard measurement of bone mineral density used by the World Health Organization. A score of -2.5 SD is the definition of osteoporosis. A Z score is the number of standard deviations from the mean bone mineral density of women in the same age group as the patient.

[51,4| I). Estrogen primarily inhibits loss of bone mass, although it can help to build a modest amount of bone mass. Weight-bearing exercise, and not swimming, is important in preventing osteoporosis. Bisphosphonates decrease the incidence of hip fractures by 30-50%.

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