Osteoporosis

Osteoporosis is a metabolic bone disease characterized by decreased bone mass and skeletal fragility.

The World Health Organization (WHO) operationally defines osteoporosis as a bone mineral density T-score less than -2.5 SD (more than 2.5 standard deviations under the young-adult mean), which is measured by dual-energy x-ray absorptiometry (DEXA), in postmenopausal women and men at least 50 years old. The reference standard site of bone mineral density analysis is the femoral neck, but other sites such as the lumbar spine can be used. A clinical diagnosis of osteoporosis may also be established without bone mineral density measurement by the presence of a fragility fracture, particularly at typical sites (spine, hip, pelvis, wrist, humerus, or rib).

Epidemiology

Risk factors

The WHO diagnostic criterion for osteoporosis is not sufficient to identify patients who are at high risk of fracture. The following risk factors, in addition to femoral neck bone mineral density, are used in FRAX (Fracture Risk Assessment Tool), which calculates a 10-year probability of major osteoporotic fracture (hip, clinical spine, humerus, or wrist fracture) and hip fracture ¹¹:

• sex (females have a higher risk)

• age (older adults have a higher risk)

• body mass index (lower body mass carries higher risk)

• prior fragility fracture

• parental history of hip fracture

• current tobacco smoking

• daily alcohol consumption of at least 3 units

• ever long-term use of oral glucocorticoids (more than 3 months at a dose equivalent to as least 5 mg daily prednisolone)

• rheumatoid arthritis

• other causes of secondary osteoporosis, including

  • type I (insulin dependent) diabetes

  • osteogenesis imperfecta in adults

  • untreated long-standing hyperthyroidism

  • hypogonadism

  • premature menopause (<45 years)

  • chronic malnutrition

  • malabsorption

  • chronic liver disease

  • HIV/AIDS, especially with some antiretroviral therapy (ART) (e.g. tenofovir disoproxil fumarate) ¹²

Clinical presentation

Osteoporosis per se is asymptomatic and is most often diagnosed when individuals are evaluated based on risk factors or following presentation with fragility fracture.

Pathology

Osteoporosis is essentially decreased bony tissue per unit volume of bone. There is no microstructural and biochemical change as occurs in osteomalacia or rickets. Hence the mineral-to-osteoid ratio is normal (cf. osteomalacia in which the mineral-to-osteoid ratio is decreased).

Osteoporosis can be localized or diffuse and be divided into:

• primary: no cause is identifiable

  • postmenopausal (type 1): occurs in 50-65-year-olds females; disproportionate loss of cancellous bone as compared to cortical bone resulting in more involvement of cancellous bone-rich areas, like vertebrae and ends of long bones

  • senile (type 2): occurs in the elderly; proportionate loss of cortical and cancellous bones affecting long bones

  • idiopathic juvenile osteoporosis

• secondary (type 3): occurs due to a range of causes including

  • endocrine disease (e.g. Cushing syndrome, hyperthyroidism, hyperparathyroidism, diabetes mellitus) ⁷

  • chronic illness (e.g. COPD, chronic liver disease, multiple sclerosis, celiac disease) ⁷

  • inflammation

  • medications (e.g. steroids, phenytoin, some ART such as tenofovir disoproxil fumarate)

  • thalassemia major ⁴

  • nutritional disturbances ⁶ (e.g. malnutrition, anorexia)

  • muscular dystrophies (e.g. Duchenne muscular dystrophy) - can be due to inherent derangement in calcium metabolism or due to steroid treatment ⁹.

There is a different list of secondary causes for juvenile osteoporosis with some overlap with adult causes. 

Radiographic features

Decreased bone density can be appreciated by decreased cortical thickness and loss of bony trabeculae in the early stages in radiography. Bones like the vertebra, long bones (proximal femur), calcaneum and tubular bones are usually looked at for evidence of osteoporosis. Nevertheless, dual energy x-ray absorptiometry (DEXA) is the gold standard of diagnosing osteoporosis ¹⁰. 

Plain radiograph

• not a sensitive modality, as more than 30-50% bone loss is required to appreciate decreased bone density on a radiograph

• vertebral osteoporosis manifests as

  • pencilling of vertebrae

  • loss of cortical bone and trabecular bone (ghost vertebra)

  • compression fractures and vertebra plana (Genant classification of vertebral fractures)

  • prominent vertical (primary) trabeculae with thinning of horizontal/secondary trabeculae in vertebral bodies

• loss of trabeculae in the proximal femur area, which is explained by Singh's index (and can also be seen in the calcaneum)

• in tubular bones (especially metacarpals), there will be thinning of the cortex

  • cortical thickness <25% of the whole thickness of the metacarpal signifies osteoporosis (normally 25-33%)

Bone mineral density measurement

Bone mineral density (BMD) measurement is the method of estimation of calcium hydroxyapatite. Multiple x-ray based, gamma-ray based and ultrasonic methods are available:

• radiographic absorptiometry (RA)

• single photon and x-ray absorptiometry (SPA)

• dual energy x-ray absorptiometry (DEXA)

  • most commonly used and most reliable

• quantitative computed tomography can be used

Based on DEXA BMD can fall into three categories ¹⁰:

• normal (low risk of fracture)

• osteopenic (medium risk)

• osteoporotic (high risk)

CT

Quantitative CT attenuation values correlate with traditional bone mineral density measurements ¹⁰. On routine CTs (performed at 120 kV), L1 vertebral body trabeculation measuring less than 90-135 HU suggests osteoporosis, with higher values in this range being more sensitive and lower values being more specific ¹³.

Ultrasound

Quantitative ultrasound of the calcaneal bone quality has emerged as a cost-efficient screening tool for osteoporosis ¹⁰. Such technological progress has made it possible to process the ultrasound signal (analysis of radio frequencies) - returning information about the microarchitecture of bone tissue, characterized by high sensitivity and specificity: it is the so-called radiofrequency echographic multi spectrometry (REMS) ¹⁴.

MRI

Bone marrow signal takes on a heterogeneous appearance with rounded focal fatty lesions replacing normal marrow with coalescence often occurring ⁵:

• T1: heterogeneously hyperintense

• T2: variable signal

Osteoporotic wedge compression fractures will alter signal characteristics depending on age.

Treatment and prognosis

Lifestyle management options include:

• adequate dietary calcium

• adequate vitamin D

• smoking cessation

• weight-bearing exercise

Pharmacological treatment options include ^8,15,16:

• bisphosphonates

  • oral: e.g. alendronate, risedronate

  • intravenous: e.g. zoledronic acid

• RANKL inhibitor: denosumab

• selective estrogen receptor modulator: raloxifene

• anabolic therapies:

  • teriparatide

  • abaloparatide

  • romosozumab

Complications

As osteoporosis decreases bone strength, patients are at an increased risk of fracture, often with minimal trauma, and commonly at the pelvis, hip and wrist.

Bisphosphonates and denosumab have been associated with rare, but serious, side effects including bisphosphonate-related atypical femoral fractures and bisphosphonate-related osteonecrosis of the jaw. 

Differential diagnosis

• ochronosis - severe osteoporosis with intervertebral disc calcifications