Osteoporosis: A Review
Osteoporosis is a major health issue affecting more than 25 million Americans, the vast majority of whom are women. Bone fractures are the major cause of morbidity and mortality associated with osteoporosis, most commonly those of the forearm, hip, and vertebral body, as well as the humerus, tibia, pelvis, and ribs. Osteoporosis-related injuries result in complications leading to prolonged hospitalization, decreased independent living, depression and lifelong disabilities, as well as having a profound effect on quality of life. More than $10 billion is spent annually treating osteoporosis and osteoporosis-related injuries. As the population continues to age, the prevalence of osteoporosis and its economic burden on society will increase further.
What is Osteoporosis?
At the macroscopic level, two types of bone tissue can be discerned. Cortical bone has a dense structure, while trabecular bone has a spongy appearance. The long bones have a thick outer layer of cortical bone with a thin inner layer of trabecular bone. The short bones, on the other hand, are composed of mainly trabecular bone with a thin layer of cortical bone. Bone is in a continuous state of remodeling involving a balance between osteoblast and osteoclast activity. Osteoblasts are cells responsible for bone formation; osteoclasts are responsible for bone resorption. Osteoporosis occurs when bone resorption is greater than bone formation, resulting in a loss of bone density. Thus, bones become brittle and susceptible to fracture.
Types of Osteoporosis
Osteoporosis can be classified as follows:
Type I, also known as Postmenopausal Osteoporosis, occurs predominately in postmenopausal women between 51 and 75 years of age. The decline in blood estrogen that occurs after menopause causes an accelerated rate of bone loss, which is characterized by an increase in trebecular bone loss. Type I osteoporosis is commonly associated with fractures of the vertebrae and distal forearm as well as increased tooth loss.
Type II, Senile Osteoporosis, occurs in both men and women over the age of 70. It is characterized by a proportional loss of both cortical and trabecular bone. Hip, pelvic and vertebral fractures are commonly associated with senile osteoporosis.
Type III, Secondary Osteoporosis, occurs equally in men and women, and at any age. This type of osteoporosis occurs secondary to other conditions, such as drug treatment or diseases.
Risk factors for the development of osteoporosis include the following: increasing age, female gender, race (Asian or Caucasian), heredity, small stature, low body weight, early menopause, oophorectomy (removal of ovaries), sedentary lifestyle, low calcium intake, excessive alcohol intake, smoking, caffeine, certain drugs, and certain predisposing medical conditions.
A simple modification of diet and lifestyle can help reduce the risk of osteoporosis in many patients. Appropriate dietary changes include a reduction of alcohol and caffeine intake and an increase in calcium intake through diet or supplementation. For premenopausal women and postmenopausal women on estrogen therapy, the daily calcium intake should be 1000 mg. Postmenopausal women who are not on estrogen therapy may benefit from 1500 mg of calcium daily.
Lifestyle adjustments such as smoking cessation, reducing alcohol consumption and increased exercise also may decrease the risk of osteoporosis. Assessment of risk factors may help identify individuals who are at increased risk and who should start preventative therapy.
Clinical Features and Diagnosis
Osteoporosis is asymptomatic until the occurrence of fractures. Fractures usually heal normally without chronic bone pain. However, accumulated skeletal deformities may result in chronic musculoskeletal pain. In cases of advanced vertebral osteoporosis, loss of height and kyphosis may develop.
Diagnosis is based on the occurrence of fractures caused by a relatively low degree of trauma and/or a low bone mineral density measurement. When the bone loss is inappropriate to the patient's age and sex, osteoporosis that is secondary to another condition (i.e. type III) should be considered.
Drugs Available for Prevention and Treatment
There are many therapeutic approaches available for the prevention and treatment of osteoporosis. However, the benefits of these treatments differ and are frequently disputed because many clinical trials have been poorly designed. The most commonly used agents are briefly described below.
Although it has been the subject of considerable debate, it seems that calcium supplementation (usually 1000 mg/day) does slow bone loss in postmenopausal women. The more soluble calcium salts appear to be the most effective. Apart from the possible increased risk of renal caliculi, tolerability is not a concern with these agents.
Hormone Replacement Therapy
Hormone replacement therapy is most effective for the prevention of osteoporosis in postmenopausal women. Estrogen receptors are present on osteoblasts. When estrogen binds to these receptors chemical mediators are secreted that inhibit the activity of osteoclasts. Initial therapy with estrogen may cause an increase in bone mass. Conjugated estrogen doses of 0.625 to 1.25 mg are effective in the prevention of osteoporosis. The greatest benefit is seen when estrogen replacement therapy is begun as soon as possible after menopause and continued throughout the remainder of life. Physicians should follow guidelines for estrogen replacement therapy in regards to other medical conditions and contraindications. Transdermal formulations are available for patients who are intolerant of oral estrogen therapy.
Bisphosphonates can also be used for the prevention and treatment of osteoporosis. These agents inhibit bone resorption and increase bone density. Included in this drug class are alendronate (Fosamax), etidronate (Didronel), and pamidronate (Aredia). These drugs differ widely in their antiresorptive potencies and of those currently available, alendronate is the most potent. Indeed, the results of recent well-controlled studies provide good evidence showing that alendronate (with or without a calcium supplement) prevents bone fractures in postmenopausal women with low bone mass. Moreover, alendronate (in conjunction with calcium supplementation and vitamin D) successfully prevented and treated loss of bone mass induced by glucocorticoids.
Patients should be informed of administration guidelines to receive full benefit from bisphosphonates. For example, alendronate must be taken with plain water first thing in the morning, and nothing else should be consumed for at least 30 minutes after the dose. The patient should also be instructed to remain upright for at least 30 minutes after administration to facilitate delivery of the drug to the stomach and to reduce the potential for esophageal irritation. Etidronate, on the other hand, must be taken on an empty stomach, 2 hours before or after a meal. The most common adverse events with bisphosphonates are gastrointestinal disturbances diarrhea and abdominal discomfort.
Of the several types of calcitonin available, salmon calcitonin appears to be the most useful. These drugs interfere with osteoclast activity, resulting in a reduction of bone resorption. Calcimar, Miacalcin, and Cibacalcin are the only agents from this class that are available in the United States at this time, and they are available only in injection form. However, a more convenient intranasal formulation of salmon calcitonin is available in some countries. These agents are useful for reducing corticosteroid-induced osteoporosis. Potential side effects of the parenteral formulations of these agents include flushing, nausea, vomiting, and pain at the injection site.
This is a selective estrogen receptor modulator (SERM) that mimics the effects of estrogen on bone without stimulatory effects on the breast or uterus. It reduces resorption of bone and decreases overall bone turnover. However, in clinical trials its effects on bone mineral density in postmenopausal women were more modest than those of conjugated estrogens. Common adverse effects of raloxifen are hot flushes and leg cramps.
This agent has been shown to stimulate osteoblast proliferation leading to a progressive increase in bone mineral density. However, it is not effective in all patients and it not possible to predict who will respond. Adverse effects of sodium fluoride include nausea and lower extremity pain associated with stress fractures.
Management of Osteoporosis
Despite the profound effect of osteoporosis on the quality of life of millions of people, preventive measures and the various treatment options can be strategically employed to minimize both the morbidity of the disease and its burden on society. The primary goal should be to ensure that optimum peak bone mass is achieved by early adulthood. Adequate dietary calcium intake, good nutrition, exercise and hormone sufficiency all contribute to this goal. The secondary goal is to maintain bone mass by means of the above measures as well as avoiding tobacco and excessive alcohol consumption. Effective management of the diseases that can cause bone loss and cautious use of certain drugs that also have this effect are other important considerations. Finally, therapeutic interventions should be used to counteract age- and menopause-related bone loss. The battle against osteoporosis is clearly a lifelong campaign.