Osteoporosis

Osteoporosis is a reduction in bone mass per unit of volume with microarchitectural deterioration of bone tissue that compromises bone strength and increases the susceptibility to fracture. It is seen primarily in elderly individuals.

EPIDEMIOLOGY OF OSTEOPOSIS

As our population has aged, the number of individu als with osteoporosis has grown to over 10 million, with an additional 34 million individuals at high risk for developing this condition. The majority of these are women (80%); one in two women will have an osteoporosis related fracture over their lifetime, and by age 75, one out of three white women will suffer an osteoporotic hip fracture. While the incidence among men is lower, one in four men over age 50 will have an osteoporosis-related fracture over their life time. Osteoporosis is responsible for 1.5 million frac tures each year, with an annual cost of approximately $17 billion. Approximately 10%/o to 20% of patients who suffer a hip fracture die of a medical complica tion within 6 months of the fracture, and those who survive are often unable to live independently.

PATHOGENESIS OF OSTEOPOROSIS

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The resorption and formation of bone is a continuous process. Under steady state, these processes are equal and linked. At around age 35, bone mass peaks, and both genders begin to lose bone mass after age 40. Estrogen receptors are present on osteoblasts, the cells that form bone, which may explain why estrogen-deficient states result in hone loss. There also appears to be an uncoupling of osteoblasts from the action of osteoclasts, the cells that resorb bone. Several different chemical modulators may mediate this uncoupling, but the precise mechanisms for developing osteoporo sis have not yet been determined.
Osteoporosis can either be primary or secondary to an underlying disease, such as hyperparathy roidism. Primary osteoporosis is an age-related bone disorder that results from aging and changes in sex hormones. It is of two types: Type I osteoporosis, or postmenopausal osteoporosis, affects women approx imately 20 years after menopause. It primarily affects trabecular bone and is due to increased osteoclast activity. Trabecular bone is present in the hip, verte brae, distal radius, and heel. Type II osteoporosis, or senile osteoporosis, involves loss of both cortical and trabecular bones and primarily affects individuals over age 70. Type II changes appear to be related to age-related decreases in calcium absorption and decreases in vitamin D absorption and synthesis. The effects of types I and 1I osteoporosis are additive and most individuals with osteoporosis have elements of both types. Secondary osteoporosis can be caused by many medical conditions and a variety of medicines, particularly glucocorticoids

CLINICAL MANIFESTATIONS OF OSTEOPOROSIS

HISTORY

Patients with osteoporosis are generally asymptomatic. However, chronic pain and tenderness over the affected area may occur, particularly in association with osteo porotic fractures_ The hones most commonly affected by osteoporotic fractures are the spine, hip, and distal radius. It is important to elicit other symptoms that may occur as complications of osteoporosis. For example, a vertebral fracture may result in spinal cord compression and neurologic findings. Osteoporosis of facet joints may also contribute to hack pain.
History is useful to identify those patients with risk factors for osteoporosis. These risk factors can be grouped into several different categories: (1) genetic: Caucasian or Asian ethnicity, small stature, and a family history of osteoporosis; (2) lifestyle: tobacco, alcohol, and caffeine consumption, lack of physical activity; (3) nutritional: low calcium and vitamin D intake; and (4) other risk fac tors such as older age and postmenopausal state.

PHYSICAL EXAMINATION

On physical examination, height reduction greater than 1.5 inches, dorsal kyphosis (dowager or widow hump), exaggerated cervical l.ordosis, gait deficits, and low body weight are common findings associated with osteoporosis. Dorsal kyphosis is due to wedge-shaped deformity in the middorsal vertebrae. Because of the risk of spinal cord compression, it is important to perform complete neurologic examination to rule out neuro 0ogic involvement from an osteoporotic fracture.

DIFFERENTIAL DIAGNOSIS

While osteoporosis is commonly age-related, other diseases or conditions may secondarily cause osteoporosis. These can be divided into five different cate gories. Identification and treatment of these underlying diseases can limit bone loss. Glucocorticoid-induced disease is the most common cause of secondary osteoporosis. When the disease or condition is not modifiable, as in patients requir ing chronic corticosteroids, the use of preventive medicines such as a bisphosphonate (e.g., alendronate) may help to prevent bone loss.

DIAGNOSTIC EVALUATION

Patients at risk for developing osteoporosis are candi dates for screening. These include (1) post menopausal women below 65 years of age with one or more risk factors besides menopause; (2) all post menopausal women over age 65; (3) postmenopausal women with a history of fractures; (4) those who are on long-term corticosteroid treatment; and more recently (5) men over age 70. In addition, those who are considering treatments or preventive measures for osteoporosis may benefit from information gained through screening. Patients being treated for osteo porosis require repeat testing to assess therapy. Measurement of bone mineral density (BMD) is the standard method for screening and establishing the diagnosis of osteoporosis. Dual energy X-ray absorp tiotnetry (DEXA) is the preferred method for con firming the diagnosis and monitoring therapy because it represents the best combination of sensitivity, tech nical simplicity reproducibility, and cost while also minimizing radiation exposure. In using DEXA to determine the effects of therapy, the same machine should be used, if possible, in order to limit variations in measurements between different DEXA scanners. BMD determinations of both the spine and hip pro vide the best assessments, since the degree of osteo porosis can differ between sites.
The BMD report provides a T score and Z score. The T score compares the patient's BMD with that of a normal adult 25 to 30 years of age and of the same gender. The Z score compares the patient's BMD with that of the same age group and gender. Osteoporosis is defined as a T score of more than 2.5 standard deviations below the mean (-2.5 SD). Osteopenia, or low bone mass, is defined as a T score between -1.0 and -2.5. Z scores of -1.5 suggest a sec ondary cause of osteoporosis. The risk for an osteo porotic fracture increases two- to fourfold for every standard deviation in reduced BMD.
In addition to a DEXA scan, blood tests are useful for identifying and managing secondary cases of osteoporosis. Initial tests consist of a complete blood count (CBC); erythrocyte sedimentation rate (ESR); 25-hydroxy vitamin D; chemistry panel including serum calcium, phosphorus, and alkaline phosphatase as well as renal function. Calcium and phosphate measurements help detect hyperparathyroidism and vitamin D deficiencies. In patients with anemia and an elevated ESR, multiple myeloma should be consid ered. Electrolyte abnormalities can identify patients with chronic acidosis or renal tubular acidosis. Serum alkaline phosphatase is a marker of osteoblastic activity and is elevated in malignancy, hyperparathyroidism, and other high-turnover states. More selective tests such as a 24-hour urine calcium tests or parathyroid hormone (PTH) levels should be selectively ordered based on history, physical examination, and preliminary laboratory findings.

TREATMENT OF OSTEOPOROSIS

The first line of prevention for osteoporosis is lifestyle changes, while pharmaceutical agents are the first line of treatment for osteoporosis. Smoking ces sation, avoiding excess alcohol, weight-bearing exer cise, and improved dietary habits are helpful in preserving bone mass. It is recommended that cal cium intake should be 1000 mg/day for premenopausal women and 1500 mg/day for postmenopausal women. Vitamin D supplementation increases bone density in patients with an established deficiency. Vitamin D deficiency has also been associated with cardiovascu lar disease, diabetes, autoimmune disease, and some types of cancer. Stores should he normalized with supplementation over a period of 2 to 3 months with repeat testing to assure adequate levels. As patients age, the risk of falls increases and fall prevention is another priority for reducing the number of osteoporotic fractures. Improving vision, adjusting sedative medications, and incorporating balance exercises are beneficial. Other environmental adjustments such as minimizing clutter, anchoring rugs, adding hand rails, and better lighting in dark hallways are helpful in preventing falls.
Preventive therapy for osteopenia should be provided to those with T score values. The bisphosphonates must be taken on an empty stomach with a large glass of water, with the patient remaining upright without eating for at least 30 minutes. More convenient for mulations that allow these medicines to be adminis tered in a single weekly dose or in a monthly dose make the therapy easier. More recently annual intra venous therapy has become available. Common side effects include stomach pain, nausea, and musculoskeletal pain. Osteonecrosis of the jaw is a very rare but serious side effect. It occurs primarily in patients with metastatic cancer or multiple myeloma who received high dose therapy.