Overview:

Osteoporosis is a skeletal condition characterized by:
- Loss of bone mineral density (BMD).
- Decreased bone strength.
- Increased susceptibility to fractures.
Predominantly affects:
- Postmenopausal women.
- Older adults.
Risk factors:
- Abrupt decrease in estrogen.
- Aging processes.
- Physical inactivity.
- Diet low in calcium and vitamin D.
- Smoking.
- Alcohol consumption.
Often asymptomatic until the first fragility fracture, typically following minor trauma.
Symptoms may include:
- Thoracic hyperkyphosis.
- Height loss due to vertebral compression fractures.
Diagnostic evaluation includes:
- Assessment of BMD (e.g., dual-energy x-ray absorptiometry).
- Fracture risk assessment.
- Workup for common causes of secondary osteoporosis.
- Conventional x-ray to confirm fractures.
Pharmacotherapy is indicated for osteoporosis:
- Bisphosphonates are the preferred first-line treatment.
  - They inhibit bone resorption and reduce fracture risk.
- Non-bisphosphonate options for those:
  - Unable to take bisphosphonates.
  - Bisphosphonate therapy has been unsuccessful.
Prevention strategies:
- Adequate calcium and vitamin D intake.
- Regular physical activity with strength-building exercises to maintain or increase bone mass and improve balance.
- Reducing the risk of falls and fragility fractures.
High-risk individuals should undergo osteoporosis screening.
- Pharmacotherapy may be considered for those with osteopenia at high risk of fractures.

Definition:

Osteoporosis: A condition characterized by the loss of trabecular and cortical bone mass, resulting in bone weakness and an elevated susceptibility to fractures.
Osteopenia: A condition marked by decreased bone strength, which is less severe than osteoporosis and indicates a lower but not critical level of bone density.

Epidemiology:

Sex: Osteoporosis is more common in females (approximately 4:1 ratio of women to men).
Age of Onset: Typically occurs between 50 and 70 years of age.
Demographics: Osteoporosis has a higher incidence in individuals with Asian, Hispanic, and northern European ancestry.

Etiology:

Primary Osteoporosis (Most Common):

Type I (Postmenopausal Osteoporosis): Occurs in postmenopausal women.
Mechanism: Estrogen stimulates osteoblasts and inhibits osteoclasts, but decreased estrogen levels after menopause lead to increased bone resorption.
Type II (Senile Osteoporosis): Involves a gradual loss of bone mass as individuals age, especially those over 70 years.
Idiopathic Osteoporosis: Can be observed in various age groups, including:
- Idiopathic Juvenile Osteoporosis.
- Idiopathic Osteoporosis in Young Adults.

Secondary Osteoporosis:

Often related to external factors or underlying medical conditions.
Drug-Induced/Iatrogenic: Frequently occurs due to long-term use of certain medications. The most common causative factor is systemic long-term corticosteroid therapy, commonly seen in patients with autoimmune diseases.
Other medications associated with secondary osteoporosis include:
- Anticonvulsants (e.g., phenytoin, carbamazepine).
- L-thyroxine.
- Anticoagulants (e.g., heparin).
- Proton pump inhibitors.
- Aromatase inhibitors (e.g., anastrozole, letrozole).
- Immunosuppressants (e.g., cyclosporine, tacrolimus).
- Androgen deprivation therapy (ADT).
Endocrine/Metabolic Factors: Conditions such as hypercortisolism, hypogonadism, hyperthyroidism, hyperparathyroidism, and renal disease can lead to secondary osteoporosis.
Multiple Myeloma: A type of cancer affecting bone marrow and contributing to bone density loss.

Additional Risk Factors:

Additional Risk Factors for Osteoporosis:

Excessive Alcohol Consumption
Cigarette Smoking
Immobilization or Inadequate Physical Activity
Malabsorption (e.g., celiac disease)
Malnutrition (e.g., diet low in calcium and vitamin D)
Anorexia
Low Body Weight
Family History of Osteoporosis
Personal History of Fracture

Clinical Features:

Clinical Presentation and Common Fractures in Osteoporosis:

Mostly Asymptomatic
Fragility Fractures: These are pathological fractures that can occur during everyday activities (e.g., bending over, sneezing) or minor trauma (e.g., falling from a standing height).
- Common Locations of Major Osteoporotic Fractures:
  - Vertebral Fractures (Most Common)
  - Femoral Neck
  - Distal Radius (Colles Fracture)
  - Other Long Bones (e.g., Humerus)
- Vertebral Compression Fractures:
  - Often Asymptomatic, but may cause acute back pain and point tenderness without neurological symptoms.
  - Multiple fractures can lead to a decreased height and the development of thoracic kyphosis.

Diagnostics:

Approach

Osteoporosis is typically detected through screening in individuals with a high risk of the condition (refer to “Screening for osteoporosis”).
Begin by assessing Bone Mineral Density (BMD) and determining the risk of experiencing a major osteoporotic fracture.
The diagnosis is confirmed if any of the following criteria for osteoporosis diagnosis are met:
- A T-score equal to or less than -2.5 standard deviations (SDs) on dual-energy x-ray absorptiometry (DXA).
- A T-score between -1 and -2.5 SDs in individuals with an increased risk of major osteoporotic fractures.
- A history of a significant osteoporotic fragility fracture, regardless of BMD.
After confirming the diagnosis:
- It is advisable to consider screening all patients for common factors that may contribute to secondary osteoporosis.
- High-risk patients should be evaluated for the presence of vertebral fractures.

Bone Mineral density(BMD) assessment:

Indications:

BMD assessment is recommended for the evaluation of suspected osteoporosis.
It’s also used for screening asymptomatic high-risk individuals for osteoporosis.
The preferred method for BMD assessment is dual-energy x-ray absorptiometry (DXA).
DXA measures BMD at the lumbar spine and hip/femoral neck using two x-ray beams. The results are presented as BMD scores, which are compared to a reference population.

BMD Scores

In postmenopausal women and men above 50 years of age, BMD is calculated using the T-score.
- A T-score of ≤ -2.5 SD indicates osteoporosis.
- A T-score between -1 and -2.5 SD indicates osteopenia.
- A T-score of ≥ -1 SD is considered normal.
For all other individuals, BMD is calculated using the Z-score.

DXA Scan in Osteopenia:

Alternatives for BMD assessment include:
- Peripheral DXA, which measures BMD at the distal forearm.
- Quantitative computed tomography (QCT), provides volumetric BMD measurements at the lumbar spine and hip. It can also assess the density of trabecular bone.

Fracture Risk Assessment:

Calculators are frequently employed in the diagnostic and screening processes for osteoporosis to assess fracture risk. One commonly used tool is FRAX, which calculates the 10-year probability of a major osteoporotic fracture.

Laboratory studies:

Routine Studies:

Routine laboratory tests for osteoporosis may include a Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), Parathyroid Hormone (PTH), phosphate, and serum 25-hydroxyvitamin D.
A 24-hour urine test may be conducted to measure levels of calcium, creatinine, and sodium.

Findings:

In cases of primary osteoporosis, typically, levels of serum calcium, phosphate, and parathyroid hormone (PTH) are within the normal range.
For secondary osteoporosis, specific laboratory findings depend on the underlying cause and are explored in detail in the section “Laboratory findings in common bone disorders.

Screening for vertebral fractures

Vertebral fractures are common in individuals with osteoporosis, and interestingly, they can be asymptomatic in up to two-thirds of cases. Nevertheless, they pose a significant risk for future fractures.

Screening Modalities [10][11]:

Vertebral Fracture Assessment (VFA): This method employs dual-energy x-ray absorptiometry (DXA) to assess for vertebral fractures.
Lateral Thoracic and Lumbar Spine X-ray: Another method used for screening vertebral fractures.

Supportive Findings (On X-ray) [18]:

When conducting an x-ray examination, certain supportive findings to look for include:
- Increased radiolucency and cortical thinning.
- Presence of vertebral compression fractures

Imaging for skeletal fractures

Indications:

Imaging is typically recommended when individuals exhibit symptoms of a fracture, such as pain and limited mobility.

Modalities:

As the first-line imaging option, plain x-rays are commonly used.
In cases where plain x-rays do not provide sufficient information, consideration of MRI or CT scans may be appropriate as a second-line option.

Supportive Findings:

When conducting imaging studies, look for supportive findings such as:
- Radiographic signs of a fracture.
  - Disruption of the bony cortex: A break in the outer layer of bone.
  - Radiolucent fracture line: A visible fracture line on imaging that appears darker or less dense due to the fracture’s presence.
- Increased radiolucency (visible on x-ray or CT scans) and cortical thinning

Treatment:

Approach

Optimize bone health for all patients.
In older patients, assess and manage risk factors for falls:
- Discuss fall prevention strategies.
- Identify and manage risk factors for falls using the CDC STEADI algorithm.
- Recommend individual and/or group exercise interventions that incorporate strength and balance training.
- Refer to physical and/or occupational therapy as needed.
Start pharmacotherapy in the following situations:
- When diagnostic criteria for osteoporosis are met.
- In patients with osteopenia at an increased risk of a major osteoporotic fracture in the next 10 years (as determined using clinical risk assessment tools such as FRAX).
For more information on fall prevention in older individuals, refer to “Introduction to geriatrics.”

Pharmacotherapy for Osteoporosis:

Indications:

Treatment: Patients who meet any of the diagnostic criteria for osteoporosis.
Prevention: Patients with osteopenia and an increased probability of a major osteoporotic fracture in the next 10 years (as determined by clinical risk assessment tools such as FRAX).

Bisphosphonates for Osteoporosis:

Indications: Preferred initial treatment for all patients.
Mechanism of Action: Inhibition of osteoclasts involved in bone resorption.
Agents: Include alendronate, risedronate, ibandronate, and zoledronic acid.
Adverse Effects:
- Osteonecrosis of the jaw.
- Atypical femoral fractures.
- Esophagitis.
- Hypocalcemia

Taking oral bisphosphonates properly is crucial to avoid potential side effects. Patients should follow these guidelines:

Oral Bisphosphonates Dosage Instructions:
- Take in the morning with a generous amount of water.
- Take at least 30 minutes before consuming food or other medications.
- After taking the medication, maintain an upright position for at least 30 minutes to prevent the risk of developing esophagitis.

Nonbisphosphonates for Osteoporosis Treatment

General Indications:

Nonbisphosphonates serve as:
- First-line alternatives for patients with contraindications to bisphosphonate therapy.
- Second-line options for individuals who do not respond well to bisphosphonates or cannot tolerate them due to adverse effects.

Specific Indications of Non-bisphosphonates:

Medication	Indications	Mechanism of Action	Potential Adverse Effects
Denosumab	– Patients with impaired renal function – Men undergoing ADT for prostate cancer	– Monoclonal antibody against RANKL, reducing osteoclast activity	– Hypocalcemia (uncommon) – Osteonecrosis of the jaw (uncommon)
PTH and PTH-Related Protein Analogue (Teriparatide, Abaloparatide)	– Patients at high or very high risk of fracture	– Synthetic parathyroid hormone, increases osteoblastic activity and bone growth	– Transitory hypercalcemia – Use with caution in patients with risk factors for osteosarcoma
Raloxifene	– Patients at increased risk of breast cancer	– Selective estrogen receptor modulator (SERM)	– Increased risk of venous thromboembolism
Calcitonin	– Postmenopausal osteoporosis (rarely used due to better alternatives)	– Inhibits bone resorption	– May increase overall cancer risk
Hormonal Therapy	– Estrogen (women): Not approved for osteoporosis treatment – Testosterone (men): Used to treat low testosterone levels in men with hypogonadism	– Estrogen: Inhibits bone remodeling – Testosterone: Inhibits bone remodeling	– Estrogen therapy: Increased risk of thromboembolism, stroke, myocardial infarction, certain cancers (e.g., breast, endometrial, ovarian)

“Estrogen is not an approved treatment for osteoporosis in women. If estrogen is prescribed to a female patient with a uterus, it should always be combined with progesterone therapy to reduce the risk of endometrial hyperplasia.

Prevention:

Enhance calcium and vitamin D intake.
Address vitamin D deficiency when present.
Promote physical activity, including strength and balance training.
Discourage or limit the following:
- Tobacco usage
- Excessive alcohol consumption
- The use of glucocorticoids

Screening:

Indications:

The following recommendations are in line with the 2018 guidelines from the US Preventive Services Task Force (USPSTF).

Screening is recommended for:

Women aged 65 and above.
Women under 65 years of age who are at an elevated risk of osteoporosis, as determined by a clinical risk assessment tool (e.g., osteoporosis risk assessment instrument, osteoporosis self-assessment tool, FRAX).

Screening Modality and Subsequent Management

Modality: Bone mineral density (BMD) assessment, with dual-energy X-ray absorptiometry (DXA) of the lumbar spine and hips being the preferred method.
If the diagnostic criteria for osteoporosis are met, it’s advisable to initiate treatment for osteoporosis.