Osteoporosis (Greek for “porous bone”) is a disease of decreased bone density leading to a predisposition to fractures. Osteoporosis is extremely common, affecting more than 200 million people worldwide. Osteoporosis is defined by having a bone mineral density that is more than 2.5 standard deviations lower than the young adult mean. Osteoporosis most commonly affects the wrist, hips, and vertebrae. Osteoporosis is more common in women, who have an accelerated loss of bone density after menopause due to the decline in estrogen, in addition to normal age-related bone loss. A pre-osteoporosis state, osteopenia, is said to be present when bone mineral density is decreased, but not to the extent that osteoporosis can be diagnosed.

Structure and Function

Osteoporosis is a disease of imbalanced bone remodeling. “Bone remodeling” refers to the biologic processes of osteoclasts removing older, worn out pieces of bone, with osteoblasts synthesizing new bone to replace them. There are two phases of bone remodeling: resorption and ossification. In the bone resorption phase, osteoclasts break down the organic tissue in bones and release minerals into the bloodstream, especially calcium, but also magnesium and phosphate. Ossification is the process of laying down new organic matrix by osteoblasts (Figure 1).

In any given year, about 10% of the adult skeleton is remodeled. Normally, osteoblast and osteoclast activity are tightly coupled to ensure maintenance of normal bone density. When osteoblasts are more active than osteoclasts, more bone is formed than resorbed and bone density increases (such as with load bearing). When osteoclasts are more active than osteoblasts, more bone is resorbed and bone density decreases.

With age, osteoblasts become less active and the osteoclasts begin to outwork the osteoblasts. Therefore, bone resorption occurs at a faster rate than bone formation and bone density is lost. Ultimately, there is increased bone fragility.

At the smallest microscopic level, the bone is apparently normal, there is just less of it (see Figure 2). Notably, very little bone has to be lost for the mechanical properties of the bone to be altered significantly. (Older readers may recall that small perforations in a checkbook or a book of stamps allow easy removal of the check or stamp, respectively – though the mass lost when making this perforation is very small, of course.)

Patient Presentation

Osteoporosis is considered a “silent” disease, in that a person can have it without symptoms and becomes aware of it only when there is a fracture. In the United States, the prototypical patient is a thin, Caucasian or Asian post-menopausal female, though osteoporosis occurs in patients of all ages, sexes, races and sizes.

The physical exam can be entirely normal in early osteoporosis. However, as the disease progresses there may be loss of vertical height and development of kyphosis in the thoracic spine (see Figure 3). More subtle loss of vertical height can be identified by asking the patient about their height and then measuring them (as most people do not mentally update their height as they age, and report their young-adult maximum).

There are three fractures (Figure 4) typically associated with osteoporosis: Colles’ fractures of the distal radius, vertebral body compression fractures, and hip fractures involving the femoral neck or intertrochanteric regions. Commonly, wrist fractures occur at age 50-60, vertebral fractures in the 60-70 window, and hip fractures after age 70.

Objective Evidence

X-rays are very insensitive for measuring bone mineral density. By the time thoracic osteoporosis can be identified on a chest x-ray, for example, approximately 50% of total bone mass has already been lost. Late in the course, a lateral chest x-ray may show anterior collapse of the thoracic vertebrae, which causes the deforming shown in Figure 2.

The U.S. Preventive Services Task Force recommends screening for women over age 65 and women of any age who have risk factors for developing osteoporosis.

Dual-energy X-ray absorptiometry (DEXA) of the hip (Figure 5) and lumbar spine is the test most frequently used to measure bone mineral density. The actual density is reported in grams/cubic centimeter, but a more useful description is a comparison to the peak bone mass achieved in young adulthood, reported as the T score.

The T score describes how many standard deviations an individual’s bone density differs from the average peak bone density of a (sex and race-matched) young adult. A T score of -1.0 means the bone is one standard deviation less dense than the average young adult, for example. Osteoporosis is diagnosed when the lumbar T score is -2.5 or lower. Osteopenia is said to be present when the value is 1 to 2.5 standard of deviations below the reference mean.

The Z score is a similar score but compares the individual to a cohort of the same age. The T score is used to diagnose or define osteoporosis whereas the Z score is used to help determine if something other than age is causing additional bone loss. For example, a healthy 65-year-old woman with menopause-related osteoporosis and no other illness may have a T score of -2.5 but the Z score may be close to 0.

In the absence of a secondary cause for osteoporosis, routine laboratory tests will be normal. If a recent fracture exists, alkaline phosphatase may be elevated due to increased bone repair and remodeling. Vitamin D, calcium, and parathyroid hormone levels should be assessed in patients sustaining low energy fragility fractures. Lab tests can be used to rule out secondary causes of osteoporosis.

Epidemiology

Osteoporosis affects more than 200 million people worldwide; there are approximately 10 million fractures per year due to osteoporosis. Although most patients with osteoporosis will be female, males can also be affected. It is estimated that in persons older than 50 years, the prevalence of osteoporosis is 15% in women and 5% in men, though this varies considerably by geography (for example, regions closer to the equator have lower fracture rates, likely on the basis of greater sunlight exposure leading to greater vitamin D synthesis).

Bone mass decreases with age (see Figure 6). Women experience an accelerated rate of loss at menopause, and thus have a distinctly higher risk at that point in the life cycle. The lifetime risk of an osteoporotic fracture is more than double for women compared to men. Within the female population, women of northern European descent have the highest risk of osteoporosis. In men, osteoporosis is most likely to be secondary to other underlying conditions such as low testosterone, alcohol abuse, smoking, and steroid use.

Differential Diagnosis

All forms of osteoporosis will have a low T score. Osteoporosis related to a secondary metabolic disorder can be differentiated from senile or postmenopausal osteoporosis by noting a low Z (age-matched) score as well as a low T score. Many underlying conditions can result in secondary osteoporosis.

Common causes of secondary osteoporosis include anorexia, chronic steroid use, HIV, hyperparathyroidism, hyperthyroidism, hypogonadism, inflammatory bowel disease and malabsorption syndromes, multiple myeloma, renal failure, rheumatoid arthritis, use of certain medications like proton pump inhibitors and anti-epileptic drugs, and vitamin D/calcium deficiency.

Red Flags

A fracture with a low-energy mechanism of injury (e.g., a wrist or hip fracture after a fall from a standing height, or vertebral fracture without any overt trauma at all) is a red flag for osteoporosis and fragility. A wrist fracture, especially, should prompt a work-up for osteoporosis, as this normally precedes the hip fracture by a few decades and timely treatment may help avert this latter complication.

Features suggesting the presence of osteoporosis include a previous fracture, excessive alcohol use, and smoking history. Loss of height and weight and changes in posture are also signals of underlying osteoporosis.

Treatment Options and Outcomes

The primary goal of osteoporosis management is prevention of adverse outcomes: reducing the risks of complications, especially fractures. Lifestyle modifications are the first step. Appropriate nutrition, weight-bearing exercise, and avoiding unhealthy habits are recommended for all patients.

In patients prone to falls, prevention programs such as exercises to improve balance (i.e., tai chi), removing area rugs and loose wires, and adequate lighting can be helpful.

Supplementation of vitamin D and calcium is recommended especially for patients with low baseline levels. Between diet and supplements, the daily intake of calcium should be at least 1200 mg/day; vitamin D should be between 800-2000 IU units daily. The dosage may be adjusted if indicated by labwork.

The pharmacological treatment of osteoporosis is divided in two categories: antiresorptive (reduces bone resorption) and anabolic (increases bone formation) agents. Among antiresorptive agents, bisphosphonates are the most commonly used class. Bisphosphonates work by inhibiting the osteoclast activity. Common side effects are upper gastrointestinal symptoms, myalgia, arthralgia, and hypocalcemia. Osteonecrosis of the jaw and atypical fractures of long bones are rare.

A special characteristic of bisphosphonates is their long-term retention in bony tissue. After 5 years of oral use or three years of IV therapy, non-high-risk patients can be given a “drug holiday” with resumption of the medication after re-evaluation in the following year.

RANK ligand inhibitors can be used as well. The RANK ligand is a protein which normally activates osteoclasts to increase bone resorption. By binding to the RANK ligand, medications in this class reduce bone resorption by preventing activation of osteoclasts. In contrast to the bisphosphonates, RANK ligand inhibitors are not retained in bony tissue for long periods and accelerated bone resorption begins very shortly after the drug is discontinued. The benefit of this class of medication is that it can be used in patients with renal dysfunction, whereas bisphosphonates might be contraindicated.

Hormone replacement therapy is not a recommended treatment for osteoporosis because of its associated risks. Estrogen is only recommended as a treatment for osteoporosis in postmenopausal women in whom other medical therapies for osteoporosis are contraindicated.

Anabolic agents, such as parathyroid hormone receptor agonists, can stimulate osteoblast activity and increase bone mineral density. These medicines are reserved for patients with severe osteoporosis and high risks of fracture.

In general, if osteoporosis is detected and treated early, prognosis is good. On the other hand, untreated osteoporosis can lead to fracture. Hip fracture, in particular, has a dismal prognosis, with about only 30% of patients returning to their pre-injury state. Vertebral fractures can also cause a loss of independence, can be painful, and can lead to a distressing loss of height.

Risk Factors and Prevention

Non-modifiable risk factors for osteoporosis include female sex, menopause, age, Caucasian race, and family history. Potentially modifiable risk factors include immobility and tobacco and alcohol use. Chronic use of certain medications (e.g., glucocorticoids and thyroid hormone) are known to cause bone mineral loss but may be unavoidable.

Bone strength develops during childhood, but bone density accumulation is not complete until the third decade of life. Peak bone mass acquired during this time will influence future risk of developing osteoporosis. Adequate nutrition with supplementation of calcium and vitamin D if necessary, normal body weight, and weight-bearing exercise can optimize bone density during this time. Avoiding excess alcohol and tobacco also plays a key role in prevention. Underlying secondary causes of bone density loss should be addressed as well.

Miscellaneous

Neurological complications from an osteoporosis-related vertebral body compression are very unlikely because the bone essentially collapses on itself– there are no bone fragments pushed into the canal to compress the cord or nerve roots.

Key Terms

Bone mineral density, Bone remodeling, Bone resorption, DEXA scan, Osteopenia, Osteoporosis

Skills

Identify patients in need of screening. Interpret bone densitometry. Master risk reduction, fall prevention, exercise, and nutritional recommendations.