Risk Reduction Data in Treatments for Osteoporosis
One-year vertebral fracture risk reduction from clinical trials in adults with postmenopausal or glucocorticoid-induced osteoporosis is reviewed. Data were obtained by conducting a literature search of osteoporosis medications using the MEDLINE database, bibliographies of selected citations, and recent meeting abstracts. The methodologic quality of the trials was assessed using recently published criteria for ranking evidence. In prospective analyses, the 1-year risk of new morphometric vertebral fractures was reduced by risedronate 5 mg/d in two 3-year studies in postmenopausal women with prevalent vertebral fracture, and in two 1-year studies in patients with or at risk for glucocorticoid-induced osteoporosis. The 1-year risk of clinical vertebral fractures was reduced by alendronate and raloxifene in post hoc analyses. Reduction of morphometrically identified vertebral fracture risk is a more stringent therapeutic goal than clinical vertebral fracture risk. Therefore, more weight should be given to data from studies that use the morphometry to assess vertebral fracture incidence.

Osteoporosis is a disorder characterized by microarchitectural deterioration of bone tissue leading to reduced bone mass, bone fragility, and an increased risk of fracture. Currently, it is estimated that 10 million people in the United States have osteoporosis, and an additional 18 million have low bone mass. In the United States, up to 30% of white postmenopausal women have osteoporosis according to World Health Organization (WHO) bone density criteria, and an additional 54% have low bone mineral density (BMD).

Aging and reduced gonadal function are common risk factors for primary osteoporosis. Declining estrogen levels at menopause result in increased bone turnover that favors resorption and loss of bone mass. Secondary osteoporosis results from conditions or drugs that accelerate bone loss. The most common cause of secondary osteoporosis is the use of long-term oral glucocorticoid therapy. Bone loss occurs even with low doses of glucocorticoids but is most rapid and extensive at prednisone doses of at least 5.0 mg/d or equivalent. Loss of bone mass is most rapid during the first year of glucocorticoid therapy in areas containing the greatest proportion of trabecular bone (ie, spine, hip, distal radius, pelvis, ribs), and significant decreases can be seen as soon as 3 months after the initiation of therapy.

Vertebral fractures are the most common type of osteoporotic fracture and are associated with deformity and morbidity. The prevalence of women with vertebral fractures increases with age, from less than 15% for patients younger than 60 years old to 32% among those aged 75 years and older. Approximately 30 to 50% of women and 20 to 30% of men develop vertebral fractures during their lifetimes, and approximately one-half of these individuals develop multiple fractures. Vertebral fractures, as detected by radiography, occur in one of six patients within 1 year of initiating long-term glucocorticoid therapy with prednisone 7.5 mg/d or its equivalent.

Clinically, vertebral fracture is suspected in patients with either back pain, vertebral deformities as assessed during a physical examination (kyphosis), or loss of height. Symptomatic or clinical vertebral fractures in osteoporotic patients are associated with pain and disability, which lead to loss of functional activity and quality of life. The risk of pain and disability increases progressively with the number and severity of vertebral deformities and is multiplied several times with each additional fracture. However, even women with asymptomatic vertebral deformities were more likely to have a history of increased back pain and back disability. These data underscore the negative impact that even asymptomatic vertebral deformities have on affected individuals.

Asymptomatic vertebral deformities are often noted on routine chest x-rays. Nearly three-fourths of vertebral deformities are asymptomatic; therefore, the only valid methods to diagnose vertebral fracture in most patients are with a standard radiograph or with lateral morphometric views obtained with the use of newer dual x-ray absorptiometry (DXA) units. Instant vertebral assessment (IVA) and lateral vertebral assessment (LVA) are new technologies using advanced fan-beam DXA to provide rapid assessment of vertebral fractures and are highly correlated with vertebral fractures, as assessed on standard lateral spine x-rays.

Once patients experience a vertebral fracture, including asymptomatic vertebral fractures, their risk of sustaining another vertebral fracture increases markedly. Patients with an existing vertebral deformity have a more than 12-fold risk during a 10-year period of sustaining another vertebral fracture as compared with control patients (ie, those without prevalent vertebral deformity). Vertebral fractures increase the risk of experiencing another vertebral fracture or other osteoporotic fractures in affected individuals. One in five postmenopausal women with a vertebral fracture will experience another vertebral fracture within the next year even while receiving calcium and vitamin D supplementation. Women with preexisting vertebral fractures have an approximate fourfold greater risk of subsequent vertebral fractures than those without prior fractures and have an increased risk of hip fracture as well. A symptomatic or an asymptomatic vertebral fracture increases the risk of subsequent hip fracture by 2.3-fold and distal forearm (Colles) fracture by 1.6-fold during a 10-year period. Mortality rates are also higher in women who experience clinical vertebral fractures.

The significant morbidity and mortality associated with vertebral fractures, the associated risk of further osteoporotic vertebral fractures in the year after initial fracture, and the high risk of this fracture during the first year of long-term glucocorticoid therapy are compelling reasons for physicians to reduce vertebral fracture risk as rapidly as possible in patients with osteoporosis. The objectives of this systematic review are to assess and summarize the literature concerning 1-year vertebral fracture risk reduction data from osteoporosis clinical trials and to make recommendations concerning treatment.