Osteoporosis is a disease of bone - leading to an increased risk of fracture. In the disease the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins is altered.

Osteoporosis is most common in women after the menopause, when it is called postmenopausal osteoporosis, but may develop in men and premenopausal women in the presence of particular hormonal disorders and other chronic diseases or as a result of smoking and medications, specifically glucocorticoids, when the disease is called steroid- or glucocorticoid-induced osteoporosis.

The disease can be prevented with lifestyle advice and medication, and preventing falls in people with known or suspected osteoporosis is an established way to prevent fractures. Osteoporosis can be treated with bisphosphonates and various other medical treatments.


Signs and symptoms

Osteoporosis itself has no specific symptoms; its main consequence is the increased risk of bone fractures. Osteoporotic fractures are those that occur in situations where healthy people would not normally break a bone; they are therefore regarded as fragility fractures. Typical fragility fractures occur in the vertebral column, hip and wrist.

The symptoms of a vertebral collapse ("compression fracture") are acute back pain, often with radiculopathic pain (shooting pain due to compression of a nerve) and rarely with spinal cord compression or cauda equina syndrome. Multiple vertebral fractures lead to a stooped posture, loss of height, and chronic pain with resultant reduction in mobility.

Fractures of the long bones acutely impair mobility and may require surgery. Hip fracture, in particular, usually requires prompt surgery, as there are serious risks associated with a hip fracture, such as deep vein thrombosis and a pulmonary embolism, and increased mortality.

The increased risk of falling associated with ageing leads to fractures of the wrist, spine and hip. The risk of falling, in turn, is increased by impaired eyesight due to any cause (e.g. glaucoma, macular degeneration), balance disorder, movement disorders (e.g. Parkinson's disease), dementia, and sarcopenia (age-related loss of skeletal muscle).

Collapse (transient loss of postural tone, with or without loss of consciousness, leads to a significant risk of falls; causes of collapse may include cardiac arrhythmias, hypotension and seizures. Removal of obstacles and loose carpets in the living environment may substantially reduce falls. Those with previous falls, as well as those with a gait or balance disorder, are most at risk.


Risk factors

Risk factors for osteoporotic fracture can be split between non-modifiable and (potentially) modifiable. In addition, there are specific diseases and disorders in which osteoporosis is a recognized complication. Medication use is theoretically modifiable, although in many cases the use of medication that increases risk of the disease is unavoidable.


Nonmodifiable

The most important risk factors for osteoporosis are advanced age (in both men and women) and female sex; oestrogen deficiency following menopause is correlated with a rapid reduction in BMD, while in men a decrease in testosterone levels has a comparable (but less pronounced) effect.

While osteoporosis occurs in people from all ethnic groups, European or Asian
ancestry predisposes for osteoporosis.

Those with a family history of fracture or osteoporosis are at an increased risk; the heritability of the fracture as well as low bone mineral density are relatively high, ranging from 25 to 80 percent. There are at least 30 genes associated with the development of osteoporosis. Those who have already had a fracture is at least twice as likely to have another fracture compared to someone of the same age and sex.


Potentially modifiable

Tobacco smoking - tobacco smoking inhibits the activity of osteoblasts, and is an independent risk factor for osteoporosis.

Low body mass index - being overweight protects against osteoporosis, either by increasing load or through the hormone leptin.

Low calcium and vitamin D intake - calcium and/or vitamin D deficiency from malnutrition increases the risk of osteoporosis. The problem occasionally arises in calcium deficient adolescents.

Alcoholism

Insufficient physical activity - bone performs remodeling in response to physical stress. People who remain physically active throughout life have a lower risk of osteoporosis. The kind of physical activity that have most effects on bone are weight bearing exercises. The bony prominences and attachments in runners are different in shape and size than those in weightlifters. Physical activity has its greatest impact during adolescence, affecting peak bone mass most. In adults, physical activity helps maintain bone mass, and can increase it by 1 or 2%. Physical fitness in later life is associated more with a decreased risk of falling than with an increased bone mineral density. Conversely, people who are bedridden are at a significantly increased risk.

Excess physical activity - excessive exercise can lead to constant damages to the bones which can cause exhaustion of the structures as described above. There are numerous examples of marathon runners who developed severe osteoporosis later in life. In females, heavy exercise leads to amenorrhea (suppression of the menstrual cycle), which is associated with decreased oestrogen levels.

Heavy metals - a strong association between cadmium, lead and bone disease has been established. Low level exposure to cadmium is associated with an increased loss of bone mineral density readily in both genders, leading to pain and increased risk of fractures, especially in elderly and in females. Higher cadmium exposure results in osteomalacia (softening of the bone).

Soft drinks - some studies indicate that soft drinks (many of which contain phosphoric acid) may increase risk of osteoporosis; others suggest soft drinks may displace calcium-containing drinks from the diet rather than directly causing osteoporosis.


Diseases and disorders

There are many disorders associated with osteoporosis:

Hypogonadal states - Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia nervosa, hypothalamic amenorrhea, hyperprolactinemia.

In females, the effect of hypogonadism is mediated by oestrogen deficiency. It can appear as early menopause (<45 years) or from prolonged premenopausal amenorrhea (>1 year). A bilateral oophorectomy (surgical removal of the ovaries) or a premature ovarian failure cause deficient estrogen production.
In males, testosterone deficiency is the cause.

Other endocrine disorders - Cushing's syndrome, hyperparathyroidism, thyrotoxicosis, hypothyroidism, insulin-dependent diabetes mellitus, acromegaly, adrenal insufficiency .

Nutritional and gastrointestinal disorders - malnutrition, parenteral nutrition, malabsorption syndromes (e.g. coeliac disease, Crohn's disease), gastrectomy, severe liver disease (especially primary biliary cirrhosis) - those with an otherwise adequate calcium intake can develop osteoporosis due to the inability to absorb calcium.

Rheumatologic disorders - rheumatoid arthritis, ankylosing spondylitis
Hematologic disorders/malignancy - multiple myeloma, lymphoma and leukemia, mastocytosis, hemophilia, thalassemia.

Inherited disorders of the bone - osteogenesis imperfecta, Marfan syndrome, hemochromatosis, hypophosphatasia, glycogen storage diseases, homocystinuria, Ehlers-Danlos syndrome, porphyria, Menkes' syndrome, epidermolysis bullosa, Gaucher's disease.

Other disorders - immobilization, scoliosis


Medication

Medication - for medication potentially causing osteoporosis, the positive effects of them needs to be compared with the degenerative effects on bone.

Steroid-induced osteoporosis (SIOP) arises due to use of glucocorticoids - analogous to Cushing's syndrome and involving mainly the axial skeleton. The synthetic glucocorticoid prescription drug prednisilone is a main candidate after prolonged intake. Some professional guidelines recommend prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially when this is in excess of three months.

Barbiturates (probably due to accelerated metabolism of vitamin D) and some other enzyme-inducing antiepileptics.

Proton pump inhibitors - these drugs inhibit the production of stomach acid; it is thought that this interferes with calcium absorption.


Diagnosis

The diagnosis of osteoporosis is made on measuring the bone mineral density (BMD). The most popular method is dual energy X-ray absorptiometry (DXA or DEXA).

In addition to the detection of abnormal BMD, the diagnosis of osteoporosis requires investigations into potentially modifiable underlying causes; this may be done with blood tests and X-rays.

Depending on the likelihood of an underlying problem, investigations for cancer with metastasis to the bone, multiple myeloma, Cushing's disease and other above mentioned causes may be performed.


Treatment with medication

Bisphosphonates are the main pharmacological measures for treatment. However, newer drugs have appeared in the 1990s, such as teriparatide and strontium ranelate.


Nutrition

Calcium

The patient should include 1200 to 1500 mg of calcium daily either via dietary means (for instance, an 8 oz glass of milk contains approximately 300 mg of calcium) or via supplementation. The body absorbs only about 500 mg of calcium at one time and so intake should be spread throughout the day.

However, the benefit of supplementation of calcium alone remains, to a degree, controversial since several nations with high calcium intakes through milk-products (e.g. the USA, Sweden) have some of the highest rates of osteoporosis worldwide, though this may be linked to such countries' excess consumption of protein. A few studies even suggested an adverse effect of calcium excess on bone density and blamed the milk industry for misleading customers. Some nutritionists assert that excess consumption of dairy products causes acidification, which leaches calcium from the system, and argue that vegetables and nuts are a better source of calcium and that in fact milk products should be avoided. This theory has no proof from scientific clinical studies. Similarly, nutritionists believe that excess caffeine consumption can also contribute to leaching calcium from the bones.

Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older. For best therapeutic effect, the recommended minimum doses are 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation). Studies that have examined the relationship between calcium supplementation and clinical fracture risk in an elderly population, showed there was a significant decrease in fracture risk in patients that received calcium supplements versus those that received placebo. However, this benefit only applied to patients who were compliant with their treatment regimen.


Vitamin D

Increasing vitamin D intake has been shown to reduce fractures up to twenty-five percent in older people, according to recent studies. The Women's Health Initiative study, however, did not find any fracture benefit from calcium and vitamin D supplementation, but these women were already taking (on average) 1200 mg/day of calcium . Muscle weakness can contribute to falls so it is beneficial for people living with osteoporosis to improve muscle function. Vitamin D deficiency causes muscle weakness.

A meta-analysis of five clinical trials showed 800 IU of vitamin D per day (plus calcium) reduced the risk of falls by 22%. A different randomized, controlled study showed nursing home residents who took 800 IU of vitamin D per day (plus calcium) having a 72% reduction in the risk of falls.

New vitamin D intake recommendations (National Osteoporosis Foundation, July 2007) are adults up to age 50, 400-800 IU daily and those over 50, 800 - 1,000 IU daily.


Excess protein

There are three elements relating to a person's levels of calcium: consumption, absorption, and excretion. High protein intake is known to encourage urinary calcium losses and has been shown to increase risk of fracture in research studies.

There is some evidence to suggest bone density benefits from taking the following supplements (in addition to calcium and vitamin D): boron, magnesium, zinc, copper, manganese, silicon, strontium, folic acid, and vitamins B6, C, and K.[31][32] This is weak evidence and quite controversial.


Exercise

Multiple studies have shown that aerobics, weight bearing, and resistance exercises can all maintain or increase BMD in postmenopausal women.

Many researchers have attempted to pinpoint which types of exercise are most effective at improving BMD and other metrics of bone quality, however results have varied. One year of regular jumping exercises appears to increase the BMD and moment of inertia of the proximal tibia in normal postmenopausal women. Treadmill walking, gymnastic training, stepping, jumping, endurance, and strength exercises all resulted in significant increases of L2-L4 BMD in osteopenic postmenopausal women. Strength training elicited improvements specifically in distal radius and hip BMD.


Prognosis

Although osteoporosis patients have an increased mortality rate due to the complications of fracture, most patients die with the disease rather than of it.

Hip fractures can lead to decreased mobility and an additional risk of numerous complications (such as deep venous thrombosis and/or pulmonary embolism, pneumonia). The 6-month mortality rate following hip fracture is approximately 13.5%, and a substantial proportion (almost 13%) of people who have suffered a hip fracture need total assistance to mobilize after a hip fracture.

Vertebral fractures, while having a smaller impact on mortality, can lead to severe chronic pain of neurogenic origin, which can be hard to control, as well as deformity. Though rare, multiple vertebral fractures can lead to such severe hunch back (kyphosis) that the resulting pressure on internal organs can impair one's ability to breathe.

Apart from risk of death and other complications, osteoporotic fractures are associated with a reduced health-related quality of life.

It is estimated that 1 in 3 women and 1 in 12 men over the age of 50 worldwide have osteoporosis. It is responsible for millions of fractures annually, mostly involving the lumbar vertebrae, hip, and wrist. Fragility fractures of ribs are also common in men.

Hip fractures are responsible for the most serious consequences of osteoporosis. In the world hip fractures are increasing between 1-3% each year, osteoporosis causes a predisposition to hip fractures -- more than 60,000 occur annually in the uk. It is estimated that a 50-year-old white woman has a 17.5% lifetime risk of fracture of the proximal femur. The incidence of hip fractures increases each decade from the sixth through the ninth for both women and men for all populations. The highest incidence is found among those men and women ages 80 or older.


For further information on osteoporosis visit The National Oseteoporosis Society on our Further Information and Support Groups page.