COPYRIGHT © by Michaelidou Maria
Dr. Maria Michailidou
Introduction: Osteoporosis & Glucocorticoid-
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, microarchitectural disruption of bone tissue, and compromised bone strength leading to an increased risk for fracture.1
1NIH Consensus Statement, Osteoporosis Prevention, Diagnosis, and Therapy, Office of the Director, Vol 17 (1), p.5, 2000.
Osteoporosis is commonly encountered in primary care settings in the management of postmenopausal women. It is often clinically silent until a fragility fracture occurs.
Osteoporotic fractures are common in postmenopausal women. Hip fractures are the
most devastating osteoporotic fractures in terms of medical, psychosocial, and financial
consequences. The lifetime probability of sustaining a hip fracture in a 50-
Osteoporosis is being recognized with increasing frequency in older men with height
loss, nontraumatic fractures, hypogonadism, and other risk factors. Fractures in
men are an important public health problem. Approximately 150,000 hip fractures occur
each year in men in the United States, accounting for about one-
Patients receiving long-
Altered microarchitecture. Decreased bone strength. Reduced bone mineral density.
Clinically, osteoporosis is diagnosed when bone mineral density (BMD) is reduced
and fractures occur due to skeletal fragility. The most common osteoporosis-
Bone loss in women begins before the onset of menopause. Typically, women lose bone mass beginning in the late third and early fourth decades. The process accelerates for the 5 to 10 years around the menopause. Postmenopausal osteoporosis results from estrogen deficiency–induced changes in the production of several key cytokines. Ultimately, this leads to an imbalance between bone formation and resorption so that resorption is favored over formation. After the increased rates of bone loss immediately surrounding the menopause cease, a less aggressive phase of bone loss ensues that continues into the eighth and ninth decades. Estrogen deficiency as well as other factors related to aging (reduced osteoprogenitor population, nutritional deficiencies, malabsorption, etc) play a role in this phase of bone loss.
Osteoporosis can be diagnosed clinically with bone densitometry or by the presence
of fragility fractures in a patient at risk for the disease. Bone densitometry has
become widely available as a diagnostic tool in recent years. Several techniques
for quantifying BMD have been developed. They include dual-
BMD by DXA has been used by the World Health Organization (WHO) to define osteopenia and osteoporosis. Their criteria are based on a large body of data on postmenopausal white women
In addition to age and BMD, a number of other clinical risk factors have been associated
with an increased incidence of osteoporotic fractures The National Osteoporosis
Foundation has categorized these factors as modifiable and nonmodifiable. Nonmodifiable
risk factors include gender, ethnicity, age, and family and/or personal history of
fracture. Modifiable risk factors include smoking, alcohol consumption, use of long-
Despite extensive information on risk factors for fracture and low BMD, no single combination—or weighting—of risk factors adequately predicts the prevalent BMD or fracture risk or can substitute for the measurement of BMD. Risk factor assessment in current practice is helpful in understanding the basis for ongoing bone loss and pointing to strategies for slowing it.
Despite the value of BMD measurements using DXA in assessing fracture risk, DXA instruments
are not available everywhere, and testing can be expensive. This has led to the need
for guidelines in recommending BMD testing. A variety of professional organizations
have published guidelines on the use of BMD testing in postmenopausal women and in
patients receiving long-
Clinical & Laboratory Evaluation
The evaluation of perimenopausal or postmenopausal women for osteoporosis or a low BMD begins with the clinical assessment. This includes the medical history with careful attention to the history of medication use (especially glucocorticoids), smoking, alcohol intake, dietary calcium intake, and family history of osteoporosis and fractures. The physical examination is focused on signs of bone pain or deformity, anemia, hyperthyroidism, hypercortisolism, malnutrition, or disorders that cause secondary forms of osteoporosis
In postmenopausal women, it is unusual to diagnose a secondary cause of osteoporosis. Most commonly estrogen deficiency is at fault. It has become apparent, however, that vitamin D deficiency and subtle forms of calcium malabsorption (eg, due to celiac sprue) are more common than previously thought and should be considered in patients with impressively low bone mass with or without fractures. In addition, multiple myeloma can be relatively "silent" clinically and present with osteoporosis, bone pain, pathologic fractures, or anemia. This diagnosis should be considered if BMD is remarkably low for age or an unexplained anemia or elevated erythrocyte sedimentation rate is present. Multiple myeloma can be easily excluded by a serum and urine protein electrophoresis. Establishing this diagnosis is important because it redirects therapy.
There has been considerable debate about what the appropriate and cost-
It is estimated that 10–20% of postmenopausal women have additional secondary causes for their bone loss although this may be a conservative estimate. Given the costs and patient commitment required for years of treatment for osteoporosis, it is imperative that underlying causes—especially those that require different management approaches—be properly diagnosed.
The ideal study to assess BMD in a postmenopausal woman is a DXA measurement of the lumbar spine and hip. In many patients over age 65, spinal BMD measurements can be spuriously elevated due to aortic calcifications, arthritis, and degenerative disc disease. In such persons, only measurements of the total hip and femoral neck are reliable enough for diagnostic purposes.
Disease Course & Complications
Postmenopausal osteoporosis can progress silently over years to a dangerously low
BMD and markedly reduced bone strength to a degree that the fracture threshold is
reached. Osteoporosis in patients taking glucocorticoids long term is characterized
by even more rapid bone loss. After this process progresses, fragility fractures
can occur with minimal impact. Fractures are the dreaded complication of osteoporosis.
Fractures of the spine cause pain but are generally self-
Hip fractures have a more dramatic course, and prognosis in the elderly osteoporotic
patient is guarded. These fractures require hospitalization and surgery. Because
of the underlying frailty of most of these patients, their comorbid conditions and
advanced age, and the prolonged immobilization and rehabilitation required, patients
who fracture their hips face decreased life expectancy. It is estimated that the
overall mortality in the first year after a hip fracture is 20%. In men, the risk
of death is three-
In addition to the medical and financial ramifications of the immediate treatment
of the hip fracture, there are substantial long-
Glucocorticoid therapy is associated with an array of potential side effects. The
most serious and disabling of these are the skeletal complications osteonecrosis
and osteoporosis. Skeletal adverse events are estimated to occur in approximately
50% of patients taking long-
The pathogenesis of glucocorticoid-
However, after a few months and continuing for years, the deleterious effects of
glucocorticoids are on the lifespan and functional capacity of osteoblasts and osteocytes.
Osteoblasts form new bone, and osteocytes are involved in mechanosensing. Apoptosis
(programmed cell death) in these populations is promoted by long-
Patients taking glucocorticoids long term are subject to an increased risk of fractures
in the spine, hip, and other sites. It has been suggested that glucocorticoid-
The majority of patients receiving glucocorticoids are taking these drugs orally.
Other routes of administration (inhaled, intranasal, or topical) are far less likely
to have the deleterious skeletal consequences of oral therapy unless particularly
high doses of long-
The differential diagnosis of low bone mass or a low BMD measurement is narrow. It
is either due to osteoporosis or osteomalacia. Any primary or secondary form of osteoporosis
described in this chapter could cause this picture. Osteomalacia causes low bone
mass or low BMD because the mineralization of the matrix is defective. Mineral content
of the skeleton (not the protein content) is reduced in osteomalacia. A host of different
conditions cause osteomalacia. These need to be considered seriously if there is
any abnormality in the levels of serum calcium, phosphorus, alkaline phosphatase,
The essentials of management for most forms of osteoporosis include the following:
Lifestyle modifications. Nutritional interventions. Pharmacologic therapies.