Osteoporosis diagnosis: laboratory tests, markers, types of surveys and tests

Reduction in bone density – the disease is virtually asymptomatic in its early stages. The main task of trauma and orthopaedic surgeon in the diagnosis of osteoporosis is an objective assessment of the patient's condition. Expert reveals the fact of pathology, finds the cause of the disease and differentiates the loss of bone mass from other similar or associated diseases, the prognosis is for recovery.

The doctor:

• clinical examination
• hardware diagnostics (x-ray, ultrasound)
• laboratory diagnostics
• genetic methods of examination.

They are All aimed at the visualization of the macro - and microarchitecture and identify the processes leading to reduction of mineral bone density.

Clinical examination

At the stage of clinical examination, the therapist may identify a group at increased risk of osteoporosis. Of the symptoms of osteoporosis your doctor may allocate a kyphotic deformity in the thoracic spine, a reduction in the growth of the patient compared with the last visit. To clinical markers of osteoporosis can also include complaints of back pain. The chance to get an appointment with the traumatologist is:

• in women with premature menopause;
• in people with a family history of osteoporosis;
• with frequent fractures under the age of 45 years;
• in patients with diseases of the collaborators of secondary osteoporosis;
• after taking a number of pharmaceutical products;
• in extraordinary thinness – anorexia, cachexia, congenital thinness with BMI less than 20.

If a person has two or more risk factors, the probability of osteoporosis is increased by one third regardless of age.

A Survey of the ward helps to detect additional risk factors:

• a deficiency of calcium in the diet
• lack of exposure to sunlight, and therefore lack of vitamin D
• problems with the stomach and intestines;
• drinking alcohol and Smoking;
• treatment with corticosteroids or hormones;
• diseases of the glands and internal organs, COPD
• prolonged immobilization or low physical activity.

Category probability OP	Clinical markers	Tactics
Identification of individuals with undoubted OP	1. The presence of fractures with minimal traumatic force in history and/or presence of radiological or clinical signs of deformed vertebrae 2. X-ray signs of OP 3. Persons older than 65 years with lower growth or thoracic kyphosis	1. Schooling OP 2. Corsets, thigh protectors 3. For back pain the time limitation in the sitting position 4. Combination preparations of calcium with vitamin D 5. Antiresorptive drugs (HRT, bisphosphonates, calcitonin, strontium ranelate)
Identify individuals with probable OP	1. Reduced growth, kyphosis of the thoracic spine 2. Persons receiving long-term corticosteroids 3. The combination of multiple risk factors over the age of 50 years	1. Schooling OP 2. Corsets, thigh protectors 3. For back pain the time limitation in the sitting position 4. Combination preparations of calcium with vitamin D 5. Antiresorptive drugs (HRT, bisphosphonates, calcitonin, strontium ranelate)
Identify individuals with probable OP and high risk of fall	Patients with risk factors in conjunction with encephalopathy, dizziness, mental illness, lonely and helpless patients are old age, neurological disease, severe CVD	1. Schooling OP 2. Corsets, thigh protectors 3. For back pain the time limitation in the sitting position 4. Combination preparations of calcium with vitamin D 5. The doctor's decision on the appointment of antiresorptive drugs (HRT, bisphosphonates, calcitonin, strontium ranelate)
Identifying individuals with high risk of developing OP	1. The presence of at least one risk factor for osteoporosis 2. The presence of somatic or other pathologies, is potentially dangerous for the development of OP 3. Hypogonadism (including women in menopause) 4. Insufficient intake of calcium	1. Schooling OP 2. Corsets, thigh protectors 3. For back pain the time limitation in the sitting position 4. Combination preparations of calcium with vitamin D

Patients with suspected osteopenia or osteoporosis is assigned to a further in-depth examination. Often the disease late-stage reveal of the trauma in patients with fractures or neurologists in patients with pain in the spine.

Orthopedist-traumatologist, neurologist or differentiate osteoporosis cancer bone injuries, osteomalacia, fibrous dysplasia, Paget's disease, peripheral neuropathy. The main base for decision making in this case is the laboratorydiagnostics.

An Obstacle to early detection of the disease are the following “clinical myths”

"the Myth"	Counterargument
osteoporosis is a disease of women in the postmenopausal period	suffer According to statistics, 1 in 3 women and 1 in 5 men over 50 years
Most cases of osteoporosis is a secondary form of the disease, as a result of heavy kollagenozov	• chronic somatic pathology in elderly approximately 80% of cases leads to a decrease of the IPC until the development of osteoporosis; • in COPD, osteopenia is found in more than 40% of patients, and when taking systemic corticosteroids, the frequency of osteopenia reaches at 85%; • when GCC is more than 68% of cases, there is osteopenia, and 50% were diagnosed OP
Relevant clinical manifestations of the disease to think about further tactics of conducting the patient	Clinical manifestations of OP (kyphotic deformation of the thoracic spine, back pain, fractures) occur most often with a significant loss such as density and mass of bone tissue. The reason for the examination of patients should focus on identifying risk factors for diseases in which the incidence of OP noted significantly more frequently. The elderly regardless of gender, at each routine inspection.

Methods of diagnosis

More than 70% of bone strength is achieved through mineral density (BMD), the remaining 30% are redistributed between the mineralization, metabolism, macro - and Microstream, microdamage. It is important to identify all defects in the early stages of the disease. For this purpose we developed a number of methods for diagnostics of osteoporosis.

Most Often osteopenia and osteoporosis using conventional x-rays detect if there are fractures or spinal deformity. At this stage already lost more than a third of bone mass. Impact on process can be when it comes to losses up to 5%. Therefore, for early detection of osteoporosis there are more accurate ways:

• ultrasonic
• isotope (mono - and bi-photons, absorbtiometry);
• mono and Energeticheskaya absorbtiometry (DXA);
• quantitative computed tomography
• blood chemistry
• genetic research materials.

The rules of wording of the diagnosis OP

Form		the Presence or absence of bone fractures	the Decrease in BMD	the Nature of the disease
OP primary	Postmenopausal, senile, idiopathic, mixed	If you have a history of fractures is a severe form of the disease	Specifies the reduction of the IPC by the T-criterion in the case of axial densitometry - worst record	Positive dynamics Stabilization Progression
OP secondary	Specifies possible cause

Ultrasound

Analysis of the mineral composition of bone using ultrasound allows you to identify areas of reduced density. This is the test for osteoporosis is based on the reflection of ultrasonic beams from the dense bodies. Introduction in clinical practice of ultrasound equipment allows to estimate mechanical properties of bone tissue. Strength and elasticity to create a hyperechogenic structure of the image.

Choice of testing method of ultrasonic densitometry (RA), usually of the heel bone and the tip of the index finger. Practice shows that this study is more suitable for screening. It is recommended to take place every 5 years for early detection of problems to women over 45 years and men older than 50.

Radiogoniometry

Accurate diagnosis is the examination of certain areas of the skeleton by energeticheskoi absorptiometry, which is considered the "gold standard" for diagnosing osteoporosis. Dual-energy x-ray absorptiometry aimed at the measurement of BMD. Diagnosis is carried out for the entire skeleton, vertebrae, or paired sections one bone. The device compares the obtained image with the reference and gives two indicators of T and Z.

T-index says about the deviations from the peak bone density of an adult, and the Z-index on the deviation from the norm for this age. In the norm T=1. Osteopenia is diagnosed when the T between -1 and -2.5, lower mineral density classified as osteoporosis. If in the anamnesis the patient has a fracture at T less than about -2.5, osteoporosis is called heavy. The decrease in BMD per unit doubles the risk of fracture. The norm for the indicator Z is also equal to 1. Additional examinations are prescribed for significant deviations Z in large or smaller parties. If the measurements are carried out at several sites, we draw attention to the worst and average performance.

bone Loss affects the entire skeleton of a man, albeit unevenly. Determine BMD in places where fractures occur most often. This:

• lumbar vertebrae
• femoral neck
• distal region of the forearm.

Women in menopause are likely to assess the condition of the vertebrae, and the elderly(over 65 years) to measure BMD of the proximal femur. DXA is prescribed for primary diagnostics of osteoporosis and evaluation of the effectiveness of therapy. Re-examined after a year.

The Survey is not harmful to health, since the intensity of irradiation is less than in conventional x-rayed 400 times. The only contraindication is pregnancy.

To DXA does not require special preparation. Eve better not to take calcium supplements. Inform the doctor about recent surveys with the use of barium. After scanning the selected area, the patient receives images and the conclusion.

Method DXA has some limitations, offset by additional studies.

CT-densitometry

With the help of computer tomography it is possible to determine a lower density and obtain a three-dimensional image of the anatomical structure of the skeleton of the plot. The study allows us to study trabecular bone structure.

For the survey with the help of computer tomography is applied in the peripheral scanner with a narrow beam, allowing to determine the mineral composition of tissue. The test is called CT-densitometry and allows to determine the local changes in mineral composition.

MRI to determine bone density

Magnetic resonance imaging was opened in 1946. The study provides a three-dimensional image of organs by registration of the radio signal, which is obtained due to the fluctuation of hydrogen atoms of water tissues in a magnetic field. For this discovery, scientists were awarded the Nobel prize.

To diagnose diseases MRI is rarely used, although the possibilities are endless. Analysis allows you to see the trabeculae of the bone very clearly. This property has been used to create scanners – devices for determining the degree of osteoporosis.

A few publications in the literature indicate the high efficiency of the study in determining bone structure. Obviously, with MRI it's possible to check the structure. However, the study is rarely used due to the high cost of the procedure.

Laboratory research

Reasons for bone loss, like osteoporosis, is not obvious. For their detection will require biochemical analysis of blood and tissue genetic research. The first is intended to:

• preventive measures in cases of metabolic disorders of remodeling and resorption of bone tissue;
• predict the rate of bone loss;
• assess the effectiveness of therapeutic methods.

At this stage, the diagnosis of osteoporosis exclude osteomalacia, bone metastases, hereditary diseases, identify causes of secondary osteoporosis, the set features the metabolism.

Doctors used in this case, three groups of biochemical markers of pathology:

1. Markers of bone formation.

   token Name	Role in bone formation	Indications for analysis	Reference values for adults and deviation
   Osteocalcin	biokompozitnyh produce the protein bone matrix secreted by osteoblasts. Concentration in blood reflects the metabolic activity of bone tissue osteoblasts	Possible prognostic indicator of strengthening bone disease	Women: >50 years – 15-46 ng/ml. Men: 30-50 years is 14-42 ng/ml; >50 years – 14-46 ng/ml
   Calcitonin	Produced by the cells of the thyroid gland: inhibits the activity of osteoclasts and thereby bone resorption; stimulates the activity of osteoblasts, synthesizing bone matrix and deposition of calcium in bones; reduces the amount of calcium in the blood, stimulating the flow in his bones; bones stimulates absorption of phosphorus and reduces the amount of phosphates in the blood; increases urinary excretion of calcium, phosphorus, sodium, magnesium, potassium, water; stimulates conversion in the kidneys inactive form of vitamin D3 into biologically active 1,25(OH)2D3 (calcitriol) in conjunction with PTH	Suspicion for thyroid disease	150 PG/ml
   Bone enzyme alkaline phosphatase (ostase)	Index of bone condition	Suspected Paget's disease, bone tumors and bone metastases, osteoporosis	• Men – to 20.1 µg/l. • Women: • premenopausal – to 14.3 mcg/l; • menopause – 22.4 µg/l
   Marker of bone matrix formation (Total P1NP)	Displays the activity of bone metabolism in the human body	performance: anabolic therapy of osteoporosis; antiresorptive therapy of osteoporosis	Women 8-80 ng/ml. Men – 10,2-95 ng/ml. Elevated level: 1. Osteoporosis. 2. Senile osteoporosis. 3. Osteomalacia. 4. Osteogenesis imperfecta. 5. Paget's Disease. 6. Of renal osteodystrophy. 7. Metastatic lesions of bone

2. Markers of status exchange. Role

   token Name	clinical research	Reference values for adults and deviation
   parathyroid hormone (PTH)	Regulates the restoration of bone tissue	Frequent fractures, presence of hypercalcemia or low content of phosphorus in the blood	Rules for men: up to 20-22 years – from 12 to 95 PG/ml; from 23 to 70 years – from 9.5 to 75 PG/ml; over 71 years – from 4.7 to 117 PG/ml. Standards in women: up to 20-22 years – from 12 to 95 PG/ml; from 23 to 70 years – from 9.5 to 75 PG/ml; over 71 years – 4.7 to 117 PG/ml. In postmenopausal OP PTH levels are often normal or low, and in senile osteoporosis and steroid-OP on the contrary slightly increased
   Calcium	Provides bone mineral density	Suspicion for hypercalcemia	Normal CA in blood: 2,15-2,50 mmol/l. In primary OP calcium levels in the blood, usually within normal limits. Possible hypercalcemia in patients with senile OP during prolonged immobilization after hip fracture
   Phosphorus	Provides bone mineral density	Suspected osteomalacia	Norma – 0,81-1,45 mmol/l. In primary OP the phosphorus level in the blood is normal, the declining trend observed in the elderly when combined OP with osteomalacia
   Vitamin D	the Regulation of calcium metabolism	Suspicion for a metabolic disorder of vitamin D in the body	Rules: from 0 to 25 nmol/l (less than 10 ng/ml) – shortage; from 25 to 75 nmol/l (10-30 ng/ml) – negative; from 75 to 250 nmol/l (30 to 100 ng/ml) – norm
   Estrogens	Stimulate the proliferation of osteocytes and enhance the processes of bone synthesis	disorders of the endocrine glands	Women 68-1655 pmol/l; post menopausal –
   Androgen			Men – 12 to 33 nmol/l
   growth Hormone somatomedin-C	Activates the synthesis of bone by stimulating osteoblasts		Adults up to 60 years: male 0-4 mcg/l; women – 0-18 μg/L. Adults 60 years and over: men – 1 to 9 µg/l; women – 1 to 16 µg/l
   Insulin	Stimulates the synthesis of bone matrix		3 to 20 mked/ml
   Thyroxine	Stimulates osteoclasts, enhancing bone resorption		About 9-19 pmol/l
   Corticosteroids	Slow down the synthesis of collagen in bone tissue		About 5-25 mcg

3. Markers of bone resorption.

   token Name	showing	Indications for study	Reference values for adults and deviation
   Veta-CrossLaps	Allows you to evaluate the rates of degradation of relatively old bone	Is used to assess the effectiveness of therapy already after the third week of treatment	Men: Less than 18 years - not detected; 18-30 years old - 155-873нг/ml; 31-50 years - 93-630 ng/ml; 51-70 years - 35-836 ng/ml; More than 70 years - not detected. Women: Less than 18 years - not detected; Premenopausal - 25-573 ng/ml; The menopause - 104-1008 ng/ml
   Bone TRAP 5b	the Degree of activity of osteoclasts		Normal levels for women up to 45 years – no more than 1,1-3,9 IU/ml for women 45-55 years – no more than 1,1-4,2 IU/ml, and for women in menopause – no more than 1.4-4,2 IU/ml. For men – normal level indicator – no more than 1,5-4,7 IU/ml

In Addition to the blood test for suspected osteoporosis, your doctor may prescribe a urinalysis to dezoksipiridinolin (DPID). The test gives information about the rate of bone resorption. Indicators for a healthy adult is presented in the table.

Sex of patient	rate DPID (nmol/mmol creatinine)
Men	2,3-5,4
Women	3,0-7,4

If the concentration of dezoksipiridinolin in the urine above the specified values, then the rate of destruction of bone tissue is higher than the rate of synthesis.

Genetic studies in osteoporosis

Today, such studies are more academic than applied. Elucidating the molecular-genetic causes of osteoporosis – the procedure is expensive and is only performed in special laboratories. The analysis to find out which gene mutation caused the disease associated with the metabolic disorder of bone tissue. Sometimes mutations do not themselves cause failures. They only serve as markers of certain hereditary processes, was found associated with mutated genes or their neighbors.

For the scientists of interest the following polymorphisms in the genes:

Col1a1 gene 1 collagen type alpha 1 (polymorphism leads to deterioration of mechanical properties of collagen);

VDR3 – receptor gene of vitamin D3 (allelic genes say about the lack of predisposition to osteoporosis (bb), moderate susceptibility (bB) and high susceptibility (BB)).

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