Osteoporosis: Causes, Symptoms, Diagnosis, and Treatment

Osteoporosis is a chronic disease affecting bone tissue, manifesting as a complex disruption of its structure and reduced density. It is not only the loss of bone mass but primarily a change in the internal organization of bones at a microscopic level: thinning of the trabecular elements, destruction of the connecting components, and deterioration of the overall bone quality.

As a result, bones become significantly more brittle and prone to fractures, even with minor injuries or falls. Fractures caused by osteoporosis pose a serious risk, often requiring prolonged recovery, leading to disability and in some cases, to fatal outcomes. The vertebrae, femoral neck, and distal radius are most commonly affected by osteoporosis.

Determining bone mineral density

The determination of bone health and osteoporosis detection is typically carried out through densitometry, a safe and relatively quick diagnostic method. Bone densitometry, also called absorptiometry, allows the determination of bone mineral density (BMD), which is the amount of minerals in a specific bone volume.

There are various types of densitometry:

• Dual-energy X-ray absorptiometry (DXA);
• Ultrasound densitometry;
• Quantitative computed tomography (QCT).

DXA is the most common and accurate method used for diagnosing osteoporosis.

According to the World Health Organization (WHO) classification, an osteoporosis diagnosis is established based on densitometry data, specifically when the T-score is equal to or less than -2.5. The T-score is an indicator that compares the patient’s bone mineral density (BMD) with the BMD of healthy individuals during peak bone mass (usually aged 25-35). It is expressed in standard deviations (SD) from the normal range.

Thus, a T-score ≤ -2.5 indicates the patient’s bone mineral density is 2.5 standard deviations or more below the peak bone mass normal value, suggesting significant density reduction and an increased fracture risk. For accurate densitometry results, it is necessary to consider the patient’s age, gender, and other factors influencing bone mass. For example, in young individuals with initially low peak bone mass, even a slight negative T-score can indicate an elevated risk of developing osteoporosis in the future.

Etiology

Osteoporosis arises from an imbalance between bone resorption (destruction) processes by osteoclasts and its formation, provided by osteoblasts. In normal conditions, these processes are balanced, maintaining constant bone renewal. In osteoporosis, destruction prevails over formation, leading to reduced density and increased bone fragility.

Various factors accelerate bone mass loss and exacerbate the condition. Among those unmodifiable are age-related changes and decreased estrogen levels in postmenopausal women. With age, in both men and women, osteoblast activity decreases and the quality of newly formed bone deteriorates, which slows down bone formation. In women, reduced estrogen production during menopause, resulting in a sharp decline in blood concentration, intensifies bone destruction by osteoclasts, as estrogens usually inhibit these cells’ activity.

Secondary causes and risk factors

Secondary causes of osteoporosis are factors that can be corrected or controlled. These include:

• Comorbidities: various chronic diseases negatively affect bone health. These include hyperthyroidism, which accelerates bone turnover and leads to bone loss; chronic renal failure, causing disrupted phosphorus metabolism and vitamin D deficiency; Cushing’s syndrome, characterized by excessive cortisol production, inhibiting osteoblast activity and enhancing bone resorption.
• Pharmacotherapy: prolonged use of certain medications may adversely affect bone tissue. The most significant risk factor is prolonged use of high-dose glucocorticoids, as they inhibit osteoblasts, decrease calcium absorption, and increase its urinary excretion. Certain antiepileptic, antiarrhythmic, and antineoplastic agents also increase the risk.
• Harmful habits: smoking and alcohol abuse have a destructive effect on bones. Nicotine impairs bone blood supply, suppresses osteoblast activity, and decreases calcium absorption. Excessive alcohol consumption disrupts calcium and vitamin D metabolism, increasing the likelihood of falls and fractures. Insufficient physical activity, especially weight-bearing exercises, also contributes to bone mass loss, as bones strengthen in response to mechanical load.
• Nutritional deficiencies: inadequate intake of calcium and vitamin D from food or malabsorption leads to a deficiency of these critical nutrients essential for bone health. Vitamin D plays a key role in calcium absorption and regulation of its blood level.
• Genetic predisposition: heredity plays a vital role in determining bone mineral density and osteoporosis risk. Mutations in specific genes may increase susceptibility to this disease. Notably, mutations in the LRP5 gene (encoding a transmembrane receptor regulating osteoblast activity) and the COL1A1 gene (encoding the α1 chain of type I collagen, the primary structural protein of bone).

Epidemiology

Osteoporosis constitutes a significant challenge for healthcare systems worldwide, particularly impacting the elderly population. It is a systemic skeletal disease characterized by reduced bone mass and compromised bone microarchitecture, leading to increased bone fragility and fracture risk even with minor injuries.

Approximately 250 million individuals globally live with this condition, with prevalence increasing with age. Annually, around 8.9 million cases of low-energy fractures are recorded. Approximately one-third of women and one-fifth of men over 50 experience osteoporosis fractures, emphasizing the disease’s public health significance.

Women are more susceptible to osteoporosis than men due to initially lower bone density, slower peak bone mass development during youth, and faster bone mass loss during menopause when decreased estrogen levels adversely affect bone tissue. The risk of osteoporosis increases with age, especially after 65, when bone resorption (destruction) processes outweigh formation processes. The highest disease prevalence is observed in North America and Europe, where higher urbanization levels, sedentary lifestyles, and vitamin D deficiency are reported, whereas rates are lower in Africa, possibly linked to a more active lifestyle and calcium-rich traditional food practices.

Hip and vertebral fractures caused by osteoporosis often lead to prolonged disability, reduced quality of life, and increased mortality among the elderly. Femoral neck fractures, for instance, require complex surgical treatment and lengthy rehabilitation and are associated with significant risk of complications such as pneumonia, thromboembolism, and pressure ulcers. Unfortunately, femoral neck fractures are associated with 20% to 24% mortality within a year post-injury, making them among the most dangerous fractures in old age. According to World Health Organization forecasts, by 2050, the number of hip fractures will increase by 310% among men and 240% among women.

Classification of osteoporosis

To better understand and organize diagnostic and treatment approaches, osteoporosis is classified into primary and secondary.

Primary osteoporosis

Primary osteoporosis develops due to natural age-related changes in the body and genetic predisposition, without identifying any obvious underlying cause other than age factors. It is divided into two main types:

Type I (postmenopausal osteoporosis): the most common form, predominantly seen in women aged 50 to 65. Its development is closely related to the sharp decline in estrogen levels following menopause. Estrogens play an important role in maintaining bone health by suppressing resorption (destruction) of bone tissue and stimulating its formation. A lack of estrogens leads to accelerated loss of trabecular bone tissue, which comprises a significant part of the vertebrae, ribs, and ends of long bones.

As a result of this type of osteoporosis, vertebral body fractures (which may cause back pain, spinal deformity, and restricted mobility) and distal metaphyseal fractures of the radius (the so-called “wrist” fracture) occur most commonly, resulting from minor injuries like falls from a small height. It is noteworthy that women with early menopause (before 45 years) or after surgical removal of the ovaries have a significantly increased risk of developing postmenopausal osteoporosis.

Type II (senile osteoporosis): develops in individuals over 70 years old, affecting both men and women. In this case, the decrease in bone density is associated with age-related decline in the function of the osteoblasts, the cells responsible for forming new bone tissue. With age, osteoblasts become less active, leading to slowed bone formation processes and, consequently, a loss of both cortical (dense, external) and trabecular bone tissue. Senile osteoporosis is characterized by an increased risk of femoral neck fractures (especially risky due to high disability likelihood and mortality rate after fracture) and pelvic bones. In men, the development of senile osteoporosis is often linked to decreased testosterone levels, which also play a crucial role in maintaining bone health.

Secondary osteoporosis

Unlike primary osteoporosis, secondary osteoporosis has a clear cause, the elimination of which may lead to bone tissue improvement. Causes of secondary osteoporosis include:

• Medications: long-term use of glucocorticosteroids can significantly reduce bone density by suppressing osteoblast activity and increasing resorption. Certain anticoagulants, antiarrhythmic agents, and some antineoplastic drugs also increase the risk of developing osteoporosis.
• Endocrine diseases: hypothyroidism (decreased function of the thyroid gland), hyperparathyroidism (increased function of the parathyroid glands), diabetes mellitus, diseases affecting the production of sex hormones (e.g., hypogonadism in men) – all these can lead to disturbances in calcium and phosphorus metabolism, which adversely affect bone health.
• Gastrointestinal diseases: diseases leading to malabsorption of nutrients, such as celiac disease, Crohn’s disease, and ulcerative colitis, can cause deficiencies of calcium and vitamin D, which are essential for bone health.
• Malignant neoplasms: certain types of cancer and bone metastases can result in the destruction of bone tissue and the development of osteoporosis. An important distinction between secondary and primary osteoporosis is the lack of prominent gender and age correlation. It can develop at any age and in both sexes, depending on the underlying cause.

Diagnosis

Accurate diagnosis of osteoporosis and selection of an optimal treatment plan require a comprehensive approach, including clinical evaluation, instrumental studies, and laboratory tests.

1. Measurement of bone density

Dual-energy X-ray absorptiometry (DXA) is considered the “gold standard” for assessing bone mineral density (BMD). This method allows precise determination of BMD in the lumbar vertebrae (L1-L4) and the femoral neck, which are the most vulnerable parts of the skeleton prone to fractures.

The obtained data are compared with normal values characteristic for a given age group and gender. Two criteria are used to assess the degree of bone mass reduction: the T-score and Z-score.

T-score: reflects the deviation of the patient’s BMD from the average value for healthy adults who have reached peak bone mass (usually at 20-30 years of age).

A T-score value of ≤ -2.5 indicates osteoporosis, which is evidence of significant bone mass loss and an increased risk of fractures. A T-score ranging from -2.5 to -1.0 corresponds to osteopenia, a condition with reduced bone density that does not meet the criteria for osteoporosis. Osteopenia is a predisposing factor for developing osteoporosis and requires lifestyle modifications and, in some cases, pharmacological treatment.

Z-score: shows the deviation of the patient’s BMD from the average value for people of the same age and gender. This criterion is more often used to assess bone mass in children, adolescents, and young adults.

2. Laboratory tests

Conducted to exclude secondary osteoporosis and associated diseases.

The following tests are performed to identify possible causes of osteoporosis and to assess the overall health status of the patient:

• Determination of calcium levels (total and ionized), phosphates, 25(OH) vitamin D (to assess vitamin D stores in the body), parathyroid hormone (PTH), thyroid-stimulating hormone (TSH) to rule out disturbances in calcium and phosphorus metabolism, as well as diseases of the thyroid and parathyroid glands.
• Determination of bone turnover markers: CTX (Beta-Cross Laps) – N-terminal telopeptide of collagen I (marker of bone resorption) and P1NP (amino-terminal propeptide of type I collagen) – marker of bone formation. High levels of these markers indicate increased bone tissue destruction.
• Blood biochemistry, including assessment of liver (ALT, AST, bilirubin) and kidney (creatinine, urea) function to evaluate the overall state of the body and exclude the impact of associated diseases on bone tissue condition.
• In certain cases, determination of sex hormone levels, such as testosterone in men and estrogens in women, is required to assess the impact of hormonal imbalance on bone tissue.

3. Imaging methods

• Spine X-ray in two projections (anterior and lateral): to detect existing vertebral body fractures and assess the degree of spinal deformation.
• Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) of the spine: to detect hidden (invisible on X-ray) fractures, compression fractures, and other pathological changes in bone tissue.
• X-ray of limb regions (e.g., femoral neck): to assess bone tissue structure and identify signs of osteoporosis.

4. Fracture risk assessment

The FRAX® online tool, developed by the World Health Organization (WHO), is used to assess the probability of fractures over ten years. This tool allows for calculating the risk of femoral neck fractures and any other fractures based on BMD data, age, gender, body mass index (BMI), and other clinical risk factors (e.g., comorbidities, smoking, alcohol consumption, family history of osteoporosis).

The results of the risk assessment help the physician determine the need for prescribing pharmacological therapy to prevent fractures.

Clinical presentation

Osteoporosis is often called the “silent disease” because bone density reduction usually proceeds unnoticed and without obvious signs at the early stages. This is due to the gradual loss of bone mass and strength, which does not cause immediate discomfort.

Initial signs of the disease in clinical practice usually present as low-energy fractures occurring with minor injuries or even spontaneously. These fractures serve as a signal of significant bone density reduction and an increased risk of recurrent fractures.

1. Vertebral body fractures often occur with minimal stress, such as bending, lifting, or even coughing. The main symptom is acute, severe back pain, which may radiate to the leg or abdomen. Over time, as the disease progresses, there may be a reduction in height (more than 4 cm compared to baseline), related to vertebral body compression. A typical feature is spinal curvature resulting from multiple fractures and vertebral column deformation, resembling a “dowager’s hump,” kyphotic deformation of the thoracic region.

2. Femoral neck fractures are the most serious complications of osteoporosis, leading to significant disability. A femoral neck fracture can occur even with minimal external impact, such as a fall from a low height (from a chair or bed) or even without any apparent cause. The main symptom is the loss of ability to move the leg normally due to severe pain and instability of the hip joint.
3. Distal radius fractures occur with minimal stress on the arm, often when extending or trying to maintain balance. The injury may occur during simple movements, such as opening a door or lifting a small object.

Multiple vertebral fractures due to osteoporosis can cause prolonged, debilitating back pain that significantly limits mobility and reduces quality of life. Changes in the shape of the spine, particularly the development of kyphosis, are also typical signs of multiple fractures. Height reduction, as with individual vertebral fractures, is associated with vertebral column compression. Such pain leads to the weakening of the back and abdominal muscles, which, in turn, increases the likelihood of new fractures and worsens spinal deformation, creating a vicious cycle.

Methods of treating osteoporosis

Treatment of osteoporosis aims to reduce fracture risk by increasing bone strength and minimizing modifiable risk factors. The treatment approach should be comprehensive and combine non-pharmacological and pharmacological methods, adapted to the patient’s individual needs and severity of the disease.

Modifying (non-pharmacological) treatment

1. Dietary supplements containing calcium and vitamin D: maintaining adequate calcium and vitamin D intake is a cornerstone of osteoporosis prevention and treatment. The recommended daily intake of calcium is 1000–1200 mg for most adults, and vitamin D is 800–1000 IU (international units). It is important to remember that calcium is better absorbed when consumed in small doses throughout the day. Sources of calcium: dairy products, green leafy vegetables (kale, spinach), enriched products. Sources of vitamin D include fatty fish (salmon, tuna, mackerel), egg yolks, enriched products, as well as sun exposure (although the effectiveness of this method depends on geographic location, time of year, and skin pigmentation).
2. Therapeutic exercise (TE): regular physical exercises, especially resistance exercises (e.g., lifting dumbbells, working out on machines, body weight exercises), play an important role in strengthening bones and improving their density (BMD). Exercises also improve muscle tone, movement coordination, and balance, which reduce the risk of falls. A combination of strength exercises (2-3 times a week) and exercises for balance and flexibility (daily) is recommended.
3. Fall prevention: falls are the main cause of fractures in people with osteoporosis. It is necessary to create a safe home environment by eliminating fall risk factors: remove high doorsteps, carpets on the floor, and slippery surfaces in the bathroom and the tub (using non-slip mats), and install handrails in the bathroom.
4. Lifestyle changes: quitting smoking and reducing alcohol consumption positively affect bone health. Nicotine disrupts the blood supply to bones, suppresses osteoblast activity, and reduces calcium absorption. Excessive alcohol consumption leads to disturbances in calcium and vitamin D metabolism, as well as increasing the risk of falls and fractures.

Pharmacological therapy

1. Bisphosphonates (alendronic acid, zoledronic acid, risedronic acid): first-line medications widely used for osteoporosis treatment. They inhibit osteoclast activity, thus reducing bone resorption and increasing its density. Bisphosphonates reduce the risk of spinal and femoral neck fractures by 40-70%. Taken orally or intravenously (zoledronic acid).
2. Denosumab: a monoclonal human antibody (IgG2) that inhibits the formation, activation, and lifespan of osteoclasts. Effectively reduces fracture risk, especially in patients for whom bisphosphonates are contraindicated or ineffective. Administered subcutaneously every 6 months.
3. Selective estrogen receptor modulators (SERM) (raloxifene): used for postmenopausal women. Raloxifene mimics the action of estrogens on bone tissue, increasing bone density and reducing fracture risk.
4. Analogs of parathyroid hormone (teriparatide): used in severe cases of osteoporosis when other treatments are ineffective. Teriparatide stimulates the formation of bone tissue by increasing osteoblast activity. It is administered subcutaneously daily. The duration of the drug application is no more than 2 years due to the risk of developing osteosarcoma.
5. Sclerostin inhibitor (Romosozumab): promotes the formation of bone tissue and also reduces resorption. The drug is administered subcutaneously once a month.
6. Hormone replacement therapy (HRT): is selectively used, mainly in women with menopausal symptoms (hot flashes, vaginal dryness) and a high risk of osteoporosis. HRT may have a positive effect on bone density, but it is associated with the risk of developing thromboembolic complications and breast cancer.
7. New treatments: new agents for the treatment of osteoporosis are being developed and researched, such as osteoanabolic antibodies (blosozumab, targeting sclerostin) and cathepsin K inhibitors (odanacatib), which show promising results in clinical trials.

Surgical therapy

In case of fractures, surgical intervention may be required to restore bone integrity and ensure its proper union. The choice of orthopedic implant and fixation method is based on radiological and radiometric data, as well as the general condition of the patient.

Find more scientifically accurate content on our social media

Subscribe and don’t miss out the latest resources

Monitoring and follow-up

It is necessary to perform BMD assessment (densitometry) every 1-2 years to evaluate treatment effectiveness and adjust therapy if needed. It is essential to maintain the pharmacological and non-pharmacological treatment regimen, assess therapy side effects, and promptly report them to the physician. Reassessment of fracture risk should also be conducted considering changes in the patient’s health status and risk factors.