( PDF ) Rev Osteoporos Metab Miner. 2018; 10 (1) Supplement: 2-4 
DOI: 10.4321/S1889-836X2018000200001

Díaz Curiel M
Enfermedades Metabólicas Óseas – Hospital Universitario Fundación Jiménez Díaz – Madrid (España)

 

Concept
Osteoporosis is the most common bone metabolic disease. It is generally defined as “systemic skeletal disease characterized by decreased bone strength with consequent increase in bone fragility and susceptibility to fractures”1. The essential elements of this definition are low bone mass and microarchitectural alteration, which distinguish osteoporosis from other bone diseases. The alteration of the microarchitecture is characterized by the loss, thinning and lack of connection between the bony trabeculae, together with a series of factors, such as alterations in the bone remodeling and the bone geometry itself, among others that have been grouped under the concept of bone quality2. On the whole, osteoporosis involves a deterioration of the structural integrity of the bone which favors skeletal fragility and causes increased risk of fractures (fx).
The World Health Organization (WHO) established an operational definition based on bone mineral density (BMD) determination in any skeletal region for white women. Thus, normal BMD values were established to those higher than -1 standard deviation (SD) in relation to the mean of young adults.
Normal (T-score > of -1); osteopenia BMD values between -1 and -2.5 SD (T-score between -1 and -2.5); osteoporosis BMD values lower than -2.5 SD (T-score below -2.5) and established osteoporosis when, together with the previous conditions, one or more osteoporotic fx is associated3.
It is important to consider that the WHO criteria should be used preferably to ascertain the epidemiology of osteoporosis and not to apply them in isolation or to indicate preventive and therapeutic measures. Although not perfect, the definition of osteoporosis according to BMD is valid, since there is a strong association between BMD and fracture risk. Prospective studies show that the decrease of a SD in BMD increases the risk of fracture between 50 and 160% (relative risk: 1.5-2.6)4.


Pathophysiology

Throughout life, bone tissue is being formed and destroyed continuously, a process known as bone remodeling, which occurs in the so-called remodeling units. Among the functions of bone remodeling are replacing old bone with new, and therefore more resistant, and participating in bone mineral homeostasis.
Osteoporosis is the result of an alteration in bone remodeling that is always due to an imbalance between the formation and bone resorption, with predominance of the latter, which leads to both the loss of bone mass and the development of microstructural alterations that we have called bone quality2.
Bone remodeling is a complex process involving mechanical and humoral factors (hormones: PTH, calcitonin, vitamin D, sex hormones, estrogens, androgens, thyroid hormones, growth hormone and corticosteroids), as well as local factors (IL-1, IL-6, TNF, M-CSF, RANKL, TGF, OPG, IGFs… etc.) and bone cells: osteoblasts, osteoclasts and osteocytes. Alterations in bone remodeling can lead to a negative balance of bone that will produce bone loss and the development of osteoporosis5-8.
The relationship between osteoblasts and osteoclasts is established by two different molecular systems that, however, contribute to the same final effect. One of them is the M-CSF growth factor, for which the osteoclasts have the c-FSM receptor. M-CSF is soluble, and therefore secreted by osteoclasts or their precursors and has an osteoclast-stimulating effect.
The other is the RANK-RANKL-OPG system9,10, mentioned above. RANK (receptor for activation of nuclear factor κκB [NFκB]) is a receptor of the TNFR family present in osteoclasts, to which the RANKL (or ligand of RANK, of the TNF family) present in the membrane of osteoblast/medullary stroma cells. As a consequence of this union, the proliferation and activity of the osteoclasts increases, while their apoptosis decreases. OPG (osteoprotegerin) is produced in the osteoblast, also a member of the TNFR family. Its ligand is RANKL itself, so it can be said that it stands between it and the RANK, thus preventing its contact. Therefore, the osteoblast produces both the activator of the osteoclasts and a substance that neutralizes this activator.
Bone quality includes a group of factors other than bone mass, which also determine bone fragility. These include structural aspects of the bone (such as the size and angle of the femoral neck) and microscopic or microstructural aspects (such as the connection between the trabeculae and the thickness thereof, as well as the mineralization of the bone, the microscopic damage that could have, the quality of collagen and osteocytes)11.

 

Clinical aspects: Fractures
Osteoporosis is a very common disease that affects 150-200 million people in the world. Approximately half of these patients belong to developed countries such as North America, Europe and Japan. In general, it is estimated that around 33% of women 50 and older will suffer from osteoporosis.
The prevalence of osteoporosis increases with age. In women between 20-44 years, the prevalence of the disease is only 0.3% while among women 70-80 years of age, the prevalence is 40%. In men, the prevalence figures are lower. Among women aged 70-80 years, only 11.3% had densitometric osteoporosis values in the lumbar spine and 2.6% in the proximal extremity of the femur 12.
As a disease, osteoporosis is asymptomatic, with fx and its complications being the only clinical manifestations of the disease13. The fx of the proximal extremity of the femur, vertebra, humerus, ribs and distal extremity of the radius or fx of Colles are considered to be typically osteoporotic14, although any fx can be produced with the exception of skull fractures.
Clinically, peripheral fx is the same as fx of the same non-osteoporotic location13,14. What distinguishes them, fundamentally, is the fact that osteoporotic fx occurs in the face of minor trauma (typically, simple fall from the standing position). For the rest, the patient also presents pain, functional limitation and deformity.

 

Epidemiology of fragility fractures
The fx constitute the clinical complication of osteoporosis. The risk of suffering a fx from 50 years on ranges in women between 39-53%, and between 13-22% in men, depending on the country under study.
The vertebral fx are the most common in patients with osteoporosis15. It is estimated that around 25 percent of women over 50 years of age will suffer one or more vertebral osteoporotic fx. The risk of vertebral fx for men is around 5.4%. Its prevalence in Spain is estimated between 17% and 23% in women over 50 years of age and somewhat less in men of the same age16. These fx can be asymptomatic, then being diagnosed accidentally when a chest x-ray is done, or also produce pain or other complications. Some of these patients develop, after the initial episode, chronic pain that worsens with prolonged standing and improves with decubitus. In addition, the vertebral fx cause a reduction in height and an alteration of the static of the spine, with kyphosis, shortening of the trunk and rectification of the lumbar lordosis, depending on the location of the fractured vertebra.
The most severe osteoporotic fx is hip fx, which in most cases occurs after a fall. The global incidence of hip fx due to osteoporosis increases with age and it is estimated that its incidence is around 2/100,000 in people under 35 years and 3,000/100,000 in people over 85 years. This translates into approximately 40,000 hip fx a year due to osteoporosis17.
The hip fx is a process that affects more women than men, the ratio between women and men is very variable in the different published series, ranging between 2 and 3.
The mortality after a hip fx is appreciable. The figures differ according to the populations studied, but range between 12% and 40% in the first year. Its incidence in Spain is estimated at around 220 cases per 100,000 inhabitants/year, although with regional variations18. The hip fx has repercussions that are immediate after the fx itself, such as surgery in 80% of cases and, in general, a long hospital stay. However, the repercussions of a hip fx are not limited to its hospital treatment, but the patients’ quality of life deteriorates considerably. Thus, most have residual disability and a percentage of cases lose the ability to lead an independent life. Only one fifth of the patients who walked without help before the fx did so six months later. The prognosis depends, in part, on the functional capacity prior to fx.
Colles’ Fx is very common, and up to 15% of women can present it during their lifetime. They present a different pattern of incidence compared with vertebral and hip fx. They predominate in the female sex in a proportion of 4:1, occurring 85% in women.
Although this fx is the least deteriorating of all osteoporotic fx, its morbidity is often underestimated. In the ECOSAP study conducted in our country19, it was observed in an outpatient population of 5,195 women over 65 years of age that the forearm fracture was 33.7% of all the fx. Colles’ fx can cause persistent pain, functional disability, neuropathy and post-traumatic arthritis, as well as being a significant risk factor for the future presentation of vertebral or hip fx.
Finally, the psychological and social impact that osteoporotic fx can engender must be taken into account. The development of depression, anxiety, fear of new fractures, and other emotional reactions are also important, and influence the recovery of patients.
To sum up, since osteoporosis is a disease closely linked to age, the demographic aging of Western countries suggests the problem will multiply. There seems to be an increase related to factors inherent in the changes in our standard of living. The incidence of fx will also increase in other areas of the planet, such as in Asia, where a large increase is expected in the 21st century 20.

Conflict of interests: The author declares that he has no conflicts of interest.

 

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