Introduction

Osteoporosis is a systemic skeletal disease characterized by reduced bone mass, deterioration of bone microarchitecture, and impaired bone strength, resulting in increased bone fragility and susceptibility to fractures. It is often referred to as a "silent disease" because it usually remains asymptomatic until a fragility fracture occurs.

Brittle bone diseases comprise a group of inherited disorders, most commonly osteogenesis imperfecta (OI), characterized by abnormalities in type I collagen synthesis or structure, leading to increased bone fragility, recurrent fractures, skeletal deformities, and varying degrees of extraskeletal manifestations. Although the underlying pathogenesis differs from osteoporosis, both conditions share similar principles of fracture prevention, optimization of bone health, and the use of antiresorptive therapy in selected patients.

Epidemiology

Osteoporosis

• One of the most common metabolic bone diseases worldwide.

• More common in postmenopausal women due to estrogen deficiency.

• Incidence increases markedly after 50 years of age.

• Also affects older men and individuals receiving long-term glucocorticoid therapy.

• Hip and vertebral fractures are associated with significant morbidity and mortality.

Brittle bone diseases

• Osteogenesis imperfecta is a rare inherited disorder.

• Usually present from infancy or childhood.

• Severity ranges from mild recurrent fractures to severe skeletal deformities.

• Most commonly inherited in an autosomal dominant pattern.

Etiology

Osteoporosis

Primary osteoporosis

• Postmenopausal osteoporosis

• Age-related (senile) osteoporosis

Secondary osteoporosis

• Long-term corticosteroid therapy

• Hyperthyroidism

• Hyperparathyroidism

• Hypogonadism

• Chronic kidney disease

• Malabsorption syndromes

• Vitamin D deficiency

• Chronic inflammatory diseases

• Alcohol misuse

• Smoking

Brittle bone diseases

Most cases are caused by inherited mutations involving genes encoding type I collagen, particularly COL1A1 and COL1A2, resulting in defective bone matrix formation.

Risk factors

Osteoporosis

• Advanced age

• Female sex

• Postmenopausal state

• Previous fragility fracture

• Family history of osteoporosis

• Low body mass index

• Physical inactivity

• Smoking

• Excess alcohol consumption

• Vitamin D deficiency

• Low dietary calcium intake

• Long-term glucocorticoid therapy

• Rheumatoid arthritis

Brittle bone diseases

• Positive family history

• Genetic mutations affecting collagen synthesis

Classification

Osteoporosis

Primary osteoporosis

• Postmenopausal

• Senile

Secondary osteoporosis

Due to identifiable medical conditions or medications.

Brittle bone diseases

Osteogenesis imperfecta is traditionally classified into several phenotypes (Types I–V), ranging from mild disease with few fractures to severe deforming disease.

Pathophysiology

Bone undergoes continuous remodeling through balanced osteoclastic bone resorption and osteoblastic bone formation. In osteoporosis, this balance is disrupted, resulting in excessive bone resorption relative to bone formation. Progressive loss of trabecular connectivity and cortical thinning reduce bone strength despite preservation of normal mineralization. Consequently, bones become increasingly susceptible to fractures after minimal trauma.

In osteogenesis imperfecta, mutations affecting type I collagen impair the quality and structural integrity of bone matrix rather than bone quantity alone. Defective collagen results in brittle bones with reduced tensile strength, predisposing patients to recurrent fractures, skeletal deformities, and impaired bone growth.

Clinical presentation

Osteoporosis

Many patients remain asymptomatic until fracture occurs.

Clinical features include:

• Fragility fractures involving the spine, hip, wrist, humerus, pelvis, or ribs

• Chronic back pain

• Progressive loss of height

• Thoracic kyphosis (dowager's hump)

• Bone pain

• Reduced mobility

• Family history of osteoporotic fracture

Brittle bone diseases

Clinical manifestations vary according to disease severity.

Features may include:

• Recurrent fractures with minimal trauma

• Bone deformities

• Short stature

• Blue sclerae

• Hearing impairment

• Joint hypermobility

• Dentinogenesis imperfecta

• Scoliosis

• Limb deformities

Diagnostic criteria

Osteoporosis

Diagnosis is established by bone mineral density measurement using dual-energy X-ray absorptiometry (DXA).

A diagnosis may also be made in patients who sustain a typical fragility fracture even if bone mineral density is not available.

Brittle bone diseases

Diagnosis is based on:

• Clinical features

• Family history

• Characteristic radiographic findings

• Genetic testing where available

Investigations

Laboratory investigations

• Complete blood count

• Serum calcium

• Serum phosphate

• Serum 25-hydroxyvitamin D

• Parathyroid hormone

• Thyroid-stimulating hormone

• Serum creatinine

• Urea

• Serum electrolytes

• Liver function tests when indicated

• Bone turnover markers (where available)

Imaging

Dual-energy X-ray absorptiometry (DXA)

Gold standard for measuring bone mineral density of the lumbar spine and hip.

Plain radiographs

Useful for detecting:

• Vertebral compression fractures

• Fragility fractures

• Skeletal deformities

• Healing fractures

Vertebral fracture assessment

Recommended in patients with height loss, kyphosis, or chronic back pain.

Differential diagnosis

• Osteomalacia

• Multiple myeloma

• Bone metastases

• Hyperparathyroidism

• Paget disease of bone

• Chronic kidney disease–mineral bone disorder

• Osteogenesis imperfecta

• Metastatic bone disease

Management

Treatment aims to:

• Prevent fractures

• Improve bone strength

• Reduce pain

• Improve functional status

• Reduce falls

• Maintain independence

Non-pharmacological management

Recommended measures include:

• Fall prevention programmes

• Regular weight-bearing and resistance exercises

• Adequate calcium intake

• Adequate vitamin D intake

• Smoking cessation

• Limiting alcohol consumption

• Exposure to sunlight where appropriate

• Nutritional optimization

• Home safety assessment

• Hip protectors in selected high-risk elderly patients

Pharmacological treatment

Pain management

Ibuprofen

• 400 mg orally immediately, then 200 mg orally every 8 hours.

OR

Meloxicam

• 7.5–15 mg orally once or twice daily for 7–14 days.

Topical analgesics

For localized pain:

Diclofenac gel

• Apply every 12 hours.

OR

Ketoprofen gel

• Apply every 12 hours.

Gastroprotection

Patients with previous peptic ulcer disease or prolonged NSAID use should receive proton pump inhibitor therapy.

Omeprazole

• 20 mg orally once daily for two weeks or longer.

OR

Pantoprazole

• 40 mg orally once daily for two weeks or longer.

Calcium supplementation

Calcium 600 mg + Vitamin D 800 IU

• Orally once daily for 3 months, then re-evaluate.

(1 microgram vitamin D = 40 IU.)

Adequate dietary calcium intake should be encouraged in addition to supplementation.

Bisphosphonate therapy

Bisphosphonates are first-line antiresorptive agents for most patients at high fracture risk.

Treatment is generally continued for 5 years, followed by reassessment of fracture risk.

Ibandronate

• 3 mg intravenously every 3 months, administered over 15–30 seconds (or according to institutional protocol), for treatment of osteoporosis.

Surgical management

Surgery is not a primary treatment for osteoporosis but is indicated for complications.

Procedures may include:

• Internal fixation of fragility fractures

• Vertebroplasty or kyphoplasty in selected vertebral compression fractures

• Total hip arthroplasty for displaced femoral neck fractures

• Corrective osteotomy for severe deformities in osteogenesis imperfecta

• Intramedullary rodding in selected children with osteogenesis imperfecta

Rehabilitation

Comprehensive rehabilitation includes:

• Progressive weight-bearing exercises

• Resistance training

• Balance training

• Physiotherapy

• Occupational therapy

• Gait training

• Fall prevention education

• Walking aids where necessary

Monitoring and follow-up

Patients should be reviewed periodically to assess:

• New fractures

• Medication adherence

• Calcium and vitamin D intake

• Adverse drug effects

• Renal function before intravenous bisphosphonates

• Repeat DXA every 1–2 years where available

• Fall risk assessment

Complications

Osteoporosis

• Vertebral compression fractures

• Hip fractures

• Wrist fractures

• Chronic pain

• Progressive kyphosis

• Reduced mobility

• Disability

• Increased mortality after hip fracture

Brittle bone diseases

• Recurrent fractures

• Skeletal deformities

• Chronic pain

• Hearing loss

• Respiratory complications

• Reduced mobility

Prognosis

Osteoporosis is a chronic but manageable disease. Early diagnosis, adequate calcium and vitamin D intake, regular exercise, and appropriate antiresorptive therapy significantly reduce fracture risk and improve long-term outcomes. Patients with osteogenesis imperfecta have variable prognoses depending on disease severity. Advances in multidisciplinary care, physiotherapy, orthopedic management, and bisphosphonate therapy have substantially improved mobility, fracture rates, and quality of life.