The risk of having osteoporosis includes age and sex. Risk factors include both non-modifiable (for example, age and some medications that may be necessary to treat a different condition) and modifiable (for example, alcohol use, smoking, and
vitamin deficiency). In addition, osteoporosis is a recognized complication of specific diseases and disorders. Medication use is theoretically modifiable, although in many cases, the use of medication that increases osteoporosis risk may be unavoidable.
Caffeine is not a risk factor for osteoporosis.
White people have a higher risk for the disease.
Non-modifiable • The most important risk factors for osteoporosis are advanced age (in both men and women) and
female sex;
estrogen deficiency following menopause or
surgical removal of the ovaries 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. • Ethnicity: While osteoporosis occurs in people from all ethnic groups,
European or
Asian ancestry predisposes to osteoporosis. • Heredity: Those with a
family history of fracture or osteoporosis are at an increased risk; the
heritability of fracture risk is 50–70%, whereas the heritability of low bone mineral density is around 60–80%. Hundreds of distinct locations on DNA have been identified as being associated with increased risk. • 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. • Build: A small stature is also a non-modifiable risk factor associated with the development of osteoporosis.
Potentially modifiable • Alcohol: Alcohol intake may increase the risk of osteoporosis. People who consume 0.5-1 drinks a day may have 1.38 times the risk compared to people who do not consume alcohol, while people who drink 2 or more glasses a day may have 1.63 times the risk. •
Vitamin D deficiency: Low circulating Vitamin D is common among the elderly worldwide. Tobacco smoking has been proposed to inhibit 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. Imbalance of
omega-6 to
omega-3 polyunsaturated fats is yet another identified risk factor. • A 2017
meta-analysis of published medical studies shows that a higher protein diet helps slightly with lower spine density but does not show significant improvement with other bones. •
Underweight/
inactive:
Bone remodeling occurs in response to physical stress, so physical inactivity can lead to significant bone loss. The incidence of osteoporosis is lower in overweight people. •
Endurance training: In female endurance athletes, large volumes of training can lead to decreased bone density and an increased risk of osteoporosis. This effect might be caused by intense training suppressing menstruation, producing
amenorrhea, and it is part of the
female athlete triad. However, for male athletes, the situation is less clear, and although some studies have reported low bone density in elite male endurance athletes, others have instead seen increased leg bone density. •
Heavy metals: A strong association between
cadmium and
lead with 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
soft drinks (many of which contain
phosphoric acid) may increase risk of osteoporosis, at least in
women. Others suggest soft drinks may displace calcium-containing drinks from the diet rather than directly causing osteoporosis. •
Proton pump inhibitors (such as
lansoprazole,
esomeprazole, and
omeprazole), which decrease the production of
stomach acid, are a risk factor for bone fractures if taken for two or more years, due to decreased absorption of
calcium in the
stomach.
Medical disorders Many diseases and disorders have been associated with osteoporosis. For some, the underlying mechanism influencing the bone metabolism is straightforward, whereas for others the causes are multiple or unknown. • In general,
immobilization causes bone loss. For example, localized osteoporosis can occur after prolonged immobilization of a fractured limb in a cast. This is also more common in active people with a high bone turnover (for example, athletes). Other examples include bone loss during
space flight or in people who are bedridden or use wheelchairs for various reasons. •
Hypogonadal states can cause secondary osteoporosis. These include
Turner syndrome,
Klinefelter syndrome,
Kallmann syndrome,
anorexia nervosa,
andropause,
acromegaly, and
adrenal insufficiency.
Crohn's disease,
ulcerative colitis, Individuals 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 micronutrients such as
vitamin K or
vitamin B12 deficiency may also contribute. • People with rheumatologic disorders such as
rheumatoid arthritis,
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. •
Chronic kidney disease can lead to
renal osteodystrophy. • Several inherited or genetic disorders have been linked to osteoporosis. These include
osteogenesis imperfecta,
Multicentric Osteolysis, Nodulosis, and Arthropathy,
Marfan syndrome, (for which it is often misdiagnosed),
glycogen storage diseases,
homocystinuria, In Parkinson's disease there may be a link between the loss of
dopaminergic neurons and altered
calcium metabolism (and
iron metabolism) causing a stiffening of the skeleton and
kyphosis.
Medication Certain medications have been associated with an increase in osteoporosis risk; only glucocorticosteroids and anticonvulsants are classically associated, but evidence is emerging concerning 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 more than three months. It is recommended to use calcium or Vitamin D as prevention. 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, similar to how thyrotoxicosis does. •
Proton pump inhibitors – these drugs inhibit the production of
stomach acid; this is thought to interfere with calcium absorption. Chronic
phosphate binding may also occur with
aluminium-containing
antacids. • Chronic
lithium therapy has been associated with osteoporosis.
Evolutionary Age-related bone loss is common among humans due to exhibiting less dense bones than other primate species. Because of the more porous bones of humans, frequency of severe osteoporosis and osteoporosis related fractures is higher. The human vulnerability to osteoporosis is an obvious cost, but it can be justified by the advantage of bipedalism, inferring that this vulnerability is the byproduct of such.
Fracture risk assessment In the absence of risk factors other than sex and age, a BMD measurement using dual-energy X-ray absorptiometry (DXA) is recommended for women at age 65. For women with risk factors, a clinical FRAX is advised at age 50.
Mechanics Osteoporosis occurs when bone mass reduction exceeds a critical threshold, with greater susceptibility to fracturing. Fractures occur when the force acting on a bone is greater than the strength of the bone. To understand the pathology of osteoporosis and skeletal degradation, studying the mechanical properties and behavior of bone is crucial, due to the under-diagnosing of osteoporosis. Mechanical properties of a material depend on the geometry and inherent structure of the materials. Bone as a material is very complex because of its hierarchical structure in which characteristics vary across length scales. At the basic scale, bone is composed of an organic matrix of collagen type-I. In another study, osteoporosis in human cancellous bone led to 3-27% variability in the stiffness and strength compared to health bone. Additionally, bone mineral density (BMD) is a parameter used to evaluate fracture risk in bones and is used as a predictor of osteoporosis. These alterations in composition contribute to how bone can handle mechanical loading. Thus, osteoporosis-induced changes at the macroscopic and microscopic levels significantly impact the mechanical properties of bone, predisposing individuals to fractures even under relatively low mechanical loads. Understanding these structural alterations is vital for developing effective diagnostic and therapeutic strategies for osteoporosis. ==Pathogenesis==