Osteoporosis

Osteoporosis ("porous bones", from Greek: ὀστέον/osteon meaning "bone" and πόρος/poros meaning "pore") is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density (BMD) is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density that is 2.5 standard deviations or more below the mean peak bone mass (average of young, healthy adults) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture. The disease may be classified as primary type 1, primary type 2, or secondary.[1] The form of osteoporosis most common in women after menopause is referred to as primary type 1 or postmenopausal osteoporosis. Primary type 2 osteoporosis or senile osteoporosis occurs after age 75 and is seen in both females and males at a ratio of 2:1. Finally, secondary osteoporosis may arise at any age and affects men and women equally. This form of osteoporosis results from chronic predisposing medical problems or disease, or prolonged use of medications such as glucocorticoids, when the disease is called steroid- or glucocorticoid-induced osteoporosis (SIOP or GIOP).

Osteoporosis risks can be reduced with lifestyle changes and sometimes medication; in people with osteoporosis, treatment may involve both. Lifestyle change includes diet and exercise, and preventing falls. Medication includes calcium, vitamin D, bisphosphonates and several others. Fall-prevention advice includes exercise to tone deambulatory muscles, proprioception-improvement exercises; equilibrium therapies may be included. Exercise with its anabolic effect, may at the same time stop or reverse osteoporosis. Osteoporosis is a component of the frailty syndrome.

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, rib, hip and wrist.

Fractures

Fractures are the most dangerous aspect of osteoporosis. Debilitating acute and chronic pain in the elderly is often attributed to fractures from osteoporosis and can lead to further disability and early mortality. The fractures from osteoporosis may also be asymptomatic. The symptoms of a vertebral collapse ("compression fracture") are sudden back pain, often with radiculopathic pain (shooting pain due to nerve root compression) 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.

Fracture Risk Calculators assess the risk of fracture based upon several criteria, including BMD, age, smoking, alcohol usage, weight, and gender. Recognised calculators include FRAX and Dubbo.

Falls risk

The increased risk of falling associated with aging 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 syncope are manifold but may include cardiac arrhythmias (irregular heart beat), vasovagal syncope, orthostatic hypotension (abnormal drop in blood pressure on standing up) 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 osteoporosis risk is unavoidable. Caffeine is not a risk factor osteoporosis.

Nonmodifiable

The most important risk factors for osteoporosis are advanced age (in both men and women) and female gender; estrogen deficiency following menopause or oophorectomy is correlated with a rapid reduction in bone mineral density, 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 are at least twice as likely to have another fracture compared to someone of the same age and sex. A small stature is also a non-modifiable risk factor associated with the development of osteoporosis.

Potentially modifiable

Excess alcohol—small amounts of alcohol do not increase osteoporosis risk and may even be beneficial, but chronic heavy drinking (alcohol intake greater than 3 units/day), especially at a younger age, increases risk significantly.

Vitamin D deficiency—low circulating Vitamin D is common among the elderly worldwide.[Mild vitamin D insufficiency is associated with increased Parathyroid Hormone (PTH) production. PTH increases bone resorption, leading to bone loss. A positive association exists between serum 1,25-dihydroxycholecalciferol levels and bone mineral density, while PTH is negatively associated with bone mineral density.

Tobacco smoking—tobacco smoking inhibits the activity of osteoblasts, and is an independent risk factor for osteoporosis. Smoking also results in increased breakdown of exogenous estrogen, lower body weight and earlier menopause, all of which contribute to lower bone mineral density.

Malnutrition—nutrition has an important and complex role in maintenance of good bone. Identified risk factors include low dietary calcium and/or phosphorus, magnesium, zinc, boron, iron, fluoride, copper, vitamins A, K, E and C (and D where skin exposure to sunlight provides an inadequate supply). Excess sodium is a risk factor. High blood acidity may be diet-related, and is a known antagonist of bone.[Some have identified low protein intake as associated with lower peak bone mass during adolescence and lower bone mineral density in elderly populations. Conversely, some have identified low protein intake as a positive factor, protein is among the causes of dietary acidity. Imbalance of omega 6 to omega 3 polyunsaturated fats is yet another identified risk factor.

High protein diet—Research has found an association between diets high in animal protein and increased urinary calcium loss from the bones.

Underweight/inactive—bone remodeling occurs in response to physical stress, and weight bearing exercise can increase peak bone mass achieved in adolescence. In adults, physical activity helps maintain bone mass, and can increase it by 1 or 2%.[citation needed] Conversely, physical inactivity can lead to significant bone loss. (Incidence of osteoporosis is lower in overweight people.)

Excess physical activity—excessive exercise can lead to constant damage 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.[who?] In women, heavy exercise can lead to decreased estrogen levels, which predisposes to osteoporosis. In addition, intensive training without proper compensatory increased nutrition increases the risk.[citation needed]

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 the 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

Many diseases and disorders have been associated with osteoporosis. For some, the underlying mechanism influencing the bone metabolism is straight-forward, whereas for others the causes are multiple or unknown.

In general, immobilization causes bone loss (following the 'use it or lose it' rule). For example, localized osteoporosis can occur after prolonged immobilization of a fractured limb in a cast. This is also more common in active patients with a high bone turn-over (for example, athletes). Other examples include bone loss during space flight or in people who are bedridden or who use wheelchairs for various reasons.

Hypogonadal states can cause secondary osteoporosis. These include Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia nervosa, andropause, hypothalamic amenorrhea or hyperprolactinemia. In females, the effect of hypogonadism is mediated by estrogen 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 (for example, andropause or after surgical removal of the testes).

Endocrine disorders that can induce bone loss include Cushing's syndrome,hyperparathyroidism,thyrotoxicosis, hypothyroidism, diabetes mellitus type 1 and 2,acromegaly and adrenal insufficiency. In pregnancy and lactation, there can be a reversible bone loss.

Malnutrition, parenteral nutrition and malabsorption can lead to osteoporosis. Nutritional and gastrointestinal disorders that can predispose to osteoporosis include coeliac disease,[ Crohn's disease, lactose intolerance, surgery (after gastrectomy, intestinal bypass surgery or bowel resection) and severe liver disease (especially primary biliary cirrhosis). Patients with bulimia can also develop osteoporosis. Those with an otherwise adequate calcium intake can develop osteoporosis due to the inability to absorb calcium and/or vitamin D. Other micro-nutrients such as vitamin K or vitamin B12 deficiency may also contribute.

Patients with rheumatologic disorders like rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus and polyarticular juvenile idiopathic arthritis are at increased risk of osteoporosis, either as part of their disease or because of other risk factors (notably corticosteroid therapy). Systemic diseases such as amyloidosis and sarcoidosis can also lead to osteoporosis.

Renal insufficiency can lead to osteodystrophy.

Hematologic disorders linked to osteoporosis are multiple myeloma and other monoclonal gammopathies, lymphoma and leukemia, mastocytosis, hemophilia, sickle-cell disease and thalassemia.

Several inherited disorders have been linked to osteoporosis. These include osteogenesis imperfecta, Marfan syndrome, hemochromatosis, hypophosphatasia, glycogen storage diseases, homocystinuria, Ehlers-Danlos syndrome, porphyria, Menkes' syndrome, epidermolysis bullosa and Gaucher's disease.

People with scoliosis of unknown cause also have a higher risk of osteoporosis. Bone loss can be a feature of complex regional pain syndrome. It is also more frequent in people with Parkinson's disease and chronic obstructive pulmonary disease.

Medication

Certain medications have been associated with an increase in osteoporosis risk; only steroids and anticonvulsants are classically associated, but evidence is emerging with regard to other drugs.

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 prednisone 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. Alternate day use may not prevent this complication.

Barbiturates, phenytoin and some other enzyme-inducing antiepileptics - these probably accelerate the metabolism of vitamin D.

L-Thyroxine over-replacement may contribute to osteoporosis, in a similar fashion as thyrotoxicosis does. This can be relevant in subclinical hypothyroidism.

Several drugs induce hypogonadism, for example aromatase inhibitors used in breast cancer, methotrexate and other anti-metabolite drugs, depot progesterone and gonadotropin-releasing hormone agonists.

Anticoagulants - long-term use of heparin is associated with a decrease in bone density, and warfarin (and related coumarins) have been linked with an increased risk in osteoporotic fracture in long-term use.

Proton pump inhibitors - these drugs inhibit the production of stomach acid; it is thought that this interferes with calcium absorption. Chronic phosphate binding may also occur with aluminium-containing antacids.

Thiazolidinediones (used for diabetes) - rosiglitazone and possibly pioglitazone, inhibitors of PPARγ, have been linked with an increased risk of osteoporosis and fracture.

Chronic lithium therapy has been associated with osteoporosis.