Osteoporosis

Introduction
Osteoporosis is a systemic skeletal disorder characterized by low bone mass and deterioration of bone microarchitecture, leading to increased bone fragility and susceptibility to fractures. It is a major public health concern worldwide, especially in postmenopausal women and older adults. The most common fracture sites are the vertebrae, hip, and distal radius.

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Epidemiology

• Affects ~200 million people globally.

• Prevalence increases with age, particularly after menopause in women due to estrogen deficiency.

• Men are also affected, but onset is typically later.

• Lifetime risk of osteoporotic fracture is estimated at ~40% for women and ~13–22% for men over 50.

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Pathophysiology
Bone strength depends on bone mass and bone quality. In osteoporosis, there is an imbalance between bone resorption (mediated by osteoclasts) and bone formation (mediated by osteoblasts), favoring resorption.

Key mechanisms:

• Postmenopausal osteoporosis: Estrogen deficiency increases osteoclast activity.

• Senile osteoporosis: Age-related decline in osteoblast function and reduced calcium/vitamin D absorption.

• Secondary osteoporosis: Due to other conditions or medications (e.g., glucocorticoids, hyperthyroidism).

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Risk Factors

Non-modifiable:

• Age >50 years.

• Female sex.

• Caucasian or Asian ethnicity.

• Family history of osteoporosis or hip fracture.

• Low body weight or small frame.

Modifiable:

• Smoking, excessive alcohol intake.

• Sedentary lifestyle.

• Low calcium/vitamin D intake.

• Chronic glucocorticoid use.

• Hypogonadism, premature menopause.

• Certain medical conditions: Hyperthyroidism, hyperparathyroidism, malabsorption syndromes, chronic kidney disease, rheumatoid arthritis.

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Clinical Features

• Often asymptomatic until a fracture occurs.

• Fragility fractures: Minimal trauma fractures, especially of the hip, vertebrae, wrist.

• Vertebral compression fractures: Acute back pain, height loss, kyphosis (“dowager’s hump”).

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Diagnosis

1. Bone Mineral Density (BMD) measurement

• Dual-energy X-ray absorptiometry (DEXA) is the gold standard.

• T-score:

  • Normal: ≥ -1.0

  • Osteopenia: -1.0 to -2.5

  • Osteoporosis: ≤ -2.5

• Z-score: Age- and sex-matched comparison (useful in younger patients).

2. Laboratory Evaluation (to rule out secondary causes)

• Serum calcium, phosphate, alkaline phosphatase.

• 25-hydroxyvitamin D.

• Renal and liver function tests.

• Thyroid-stimulating hormone (TSH).

• Parathyroid hormone (PTH).

• CBC, ESR/CRP (if inflammatory disease suspected).

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Management

1. Lifestyle and General Measures

• Adequate calcium intake: 1,000–1,200 mg/day (diet + supplements).

• Adequate vitamin D intake: 800–1,000 IU/day (supplementation if deficient).

• Weight-bearing and muscle-strengthening exercises.

• Smoking cessation, limit alcohol (<2 units/day).

• Fall prevention strategies (home safety, vision correction, balance training).

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2. Pharmacologic Therapy
Indications:

• T-score ≤ -2.5 at spine, hip, or femoral neck.

• Osteopenia (T-score -1.0 to -2.5) with high fracture risk (FRAX score ≥20% major fracture or ≥3% hip fracture).

• Prior fragility fracture.

a. Anti-resorptive agents

• Bisphosphonates (first-line):

  • Alendronate: 70 mg orally once weekly.

  • Risedronate: 35 mg orally once weekly or 150 mg monthly.

  • Ibandronate: 150 mg orally monthly or 3 mg IV every 3 months.

  • Zoledronic acid: 5 mg IV yearly.

  • Instructions: Take oral forms with water, remain upright for ≥30 min, empty stomach.

• Denosumab (RANKL inhibitor):

  • 60 mg subcutaneous every 6 months.

  • Suitable for patients intolerant to bisphosphonates or with renal impairment.

• Selective Estrogen Receptor Modulators (SERMs):

  • Raloxifene: 60 mg orally daily; reduces vertebral fracture risk; beneficial in women at risk of breast cancer.

b. Anabolic agents (stimulate bone formation)

• Teriparatide (recombinant PTH 1-34): 20 mcg SC daily for up to 2 years; indicated for severe osteoporosis or bisphosphonate failure.

• Abaloparatide: Similar to teriparatide; 80 mcg SC daily for up to 2 years.

• Romosozumab (sclerostin inhibitor): 210 mg SC monthly for 12 months; followed by anti-resorptive therapy.

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3. Monitoring

• DEXA scan every 1–2 years to assess response.

• Monitor calcium, vitamin D, and renal function during therapy.

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Complications

• Fragility fractures, leading to disability and reduced quality of life.

• Chronic pain, deformity from vertebral fractures.

• Increased mortality after hip fracture.

• Rare adverse effects of therapy: Osteonecrosis of the jaw, atypical femoral fractures (bisphosphonates); hypocalcemia (denosumab).

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Prognosis

• With early diagnosis, lifestyle modification, and appropriate treatment, fracture risk can be significantly reduced.

• However, untreated osteoporosis can result in progressive bone loss and recurrent fractures.